Substances that are recognized by the immune system and induce an immune reaction.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Substances elaborated by bacteria that have antigenic activity.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
Substances elaborated by viruses that have antigenic activity.
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.
Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
Antibodies produced by a single clone of cells.
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.
Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Tetraspanin proteins found at high levels in cells of the lymphoid-myeloid lineage. CD53 antigens may be involved regulating the differentiation of T-LYMPHOCYTES and the activation of B-LYMPHOCYTES.
A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.
Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Substances of fungal origin that have antigenic activity.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The major group of transplantation antigens in the mouse.
A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.
Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Glycoproteins found on the membrane or surface of cells.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Sites on an antigen that interact with specific antibodies.
A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.
A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.
Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.
Established cell cultures that have the potential to propagate indefinitely.
A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.
Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Progenitor cells from which all blood cells derive.
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
Tetraspanin proteins that are involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Proteins prepared by recombinant DNA technology.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.
Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.
Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.
A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.
An encapsulated lymphatic organ through which venous blood filters.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.
A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
A widely distributed cell surface transmembrane glycoprotein that stimulates the synthesis of MATRIX METALLOPROTEINASES. It is found at high levels on the surface of malignant NEOPLASMS and may play a role as a mediator of malignant cell behavior.
A general term for various neoplastic diseases of the lymphoid tissue.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A widely expressed transmembrane glycoprotein that functions as a METASTASIS suppressor protein. It is underexpressed in a variety of human NEOPLASMS.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A cell line derived from cultured tumor cells.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.
A cell adhesion molecule of the immunoglobulin superfamily that is expressed in ENDOTHELIAL CELLS and is involved in INTERCELLULAR JUNCTIONS.
Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Antibodies obtained from a single clone of cells grown in mice or rats.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
A heterodimeric protein that is a cell surface antigen associated with lymphocyte activation. The initial characterization of this protein revealed one identifiable heavy chain (ANTIGENS, CD98 HEAVY CHAIN) and an indeterminate smaller light chain. It is now known that a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS) can dimerize with the heavy chain. Depending upon its light chain composition a diverse array of functions can be found for this protein. Functions include: type L amino acid transport, type y+L amino acid transport and regulation of cellular fusion.
The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
The sum of the weight of all the atoms in a molecule.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.
Immunoglobulins produced in response to VIRAL ANTIGENS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
A glycolipid, cross-species antigen that induces production of antisheep hemolysin. It is present on the tissue cells of many species but absent in humans. It is found in many infectious agents.
Elements of limited time intervals, contributing to particular results or situations.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).

Effect of transforming growth factor beta on experimental Salmonella typhimurium infection in mice. (1/2090)

We have investigated the effect of the in vivo administration of recombinant transforming growth factor beta (rTGF-beta) on the pathogenic mechanisms involved in Salmonella typhimurium experimental infection in mice. The protective response elicited by macrophages was induced by rTGF-beta1 by 2 days after experimental infection, as demonstrated by an increased NO production, while the humoral protective effect began with cytokine mRNA expression 2 days after the challenge and continued after 5 days with cytokine release and lymphocyte activation. We demonstrated that all mice who received rTGF-beta1 survived 7 days after infection. The number of bacteria recovered in the spleens and in the livers of rTGF-beta1-treated mice 2 and 5 days after infection was significantly smaller than that found in the same organs after phosphate-buffered saline (PBS) inoculation. Furthermore, 2 and 5 days after infection, splenic macrophages from rTGF-beta1-treated mice showed a greater NO production than did those from PBS-treated mice. The effect of rTGF-beta1 on S. typhimurium infection in mice was correlated with the expression of cell costimulatory CD28 molecules. Five days after S. typhimurium infection, the percentage of CD28(+)-expressing T cells in splenic lymphocytes from rTGF-beta1-treated mice increased with respect to that from control mice. Gamma interferon (IFN-gamma) mRNA was present in a greater amount in spleen cells from rTGF-beta1-treated mice after 2 days, although the intensity of the band decreased 5 days after the challenge. A similar pattern was obtained with the mRNAs for interleukin-1alpha (IL-1alpha), IL-6, TGF-beta, and inducible nitric oxide synthase, which showed greater expression in cells obtained from rTGF-beta1-treated and S. typhimurium-infected mice 2 days after challenge. The treatment with rTGF-beta1 induced an increase in IL-1alpha and IFN-gamma release in the supernatant of splenocyte cultures 5 days after the experimental infection with S. typhimurium. Moreover, we demonstrated that 5 days after infection, the IFN-gamma titer was significantly greater in the sera of rTGF-beta-treated mice than in those of PBS-treated mice. Also, hsp60 showed greater expression 2 days after the challenge in splenocytes from rTGF-beta1-treated mice. The role played by proinflammatory and immunoregulatory cytokines and by CD28 is discussed.  (+info)

Expanded tumor-reactive CD4+ T-cell responses to human cancers induced by secondary anti-CD3/anti-CD28 activation. (2/2090)

Generation of tumor-reactive T cells in large numbers ex vivo is a requisite step in the adoptive immunotherapy of patients. We examined the immune responses of T cells derived from tumor vaccine-primed lymph nodes activated with anti-CD3 alone and with an anti-CD3/anti-CD28 combination. Nylon wool-purified CD3+ cells were isolated from vaccine-primed lymph nodes obtained from melanoma, renal cell, and head and neck cancer patients. In the absence of antigen-presenting cells, activation with anti-CD3/anti-CD28 greatly enhanced subsequent T-cell expansion in interleukin 2 (>100-fold), compared to anti-CD3 alone. CD4+ T cells were preferentially stimulated. In four of eight patients, we found evidence of CD4+ cellular responses to autologous tumors by cytokine release assays. Positively selected CD4+ cells activated with anti-CD3/anti-CD28 released greater amounts of cytokine (IFN-gamma and granulocyte macrophage colony-stimulating factor) in response to autologous tumors compared to cells activated by anti-CD3 alone. The CD4+ reactivity was MHC class II restricted and appeared to be associated with the expression of class II molecules on the vaccinating tumor cells. The CD4+ T-cell responses to class II-restricted tumor-associated antigens in patients with renal cell cancers represent unique findings.  (+info)

CD28 ligation induces tyrosine phosphorylation of Pyk2 but not Fak in Jurkat T cells. (3/2090)

Protein tyrosine kinases are critical for the function of CD28 in T cells. We examined whether the tyrosine kinases Pyk2 and Fak (members of the focal adhesion kinase family) are involved in CD28 signaling. We found that ligating CD28 in Jurkat T cells rapidly increases the tyrosine phosphorylation of Pyk2 but not of Fak. Paxillin, a substrate for Pyk2 and Fak, was not tyrosine-phosphorylated after CD28 ligation. CD28-induced tyrosine phosphorylation of Pyk2 was markedly reduced in the absence of external Ca2+. Previous studies have shown that the T cell antigen receptor (TCR) induces tyrosine phosphorylation of Pyk2. In this report, the concurrent ligation of CD28 and TCR increased tyrosine phosphorylation of Pyk2; however, the extent of phosphorylation by both receptors was equivalent to the sum of that induced by each receptor alone. The Syk/Zap inhibitor piceatannol blocked CD28, and TCR induced tyrosine phosphorylation of Pyk2, suggesting that Syk/Zap is involved in Pyk2 phosphorylation. In contrast, the phosphatidylinositol 3-kinase inhibitor wortmannin blocked TCR- but not CD28-induced phosphorylation of Pyk2, suggesting that CD28 and TCR activate distinct pathways to induce tyrosine phosphorylation of Pyk2. Notably, depleting phorbol 12-myristate 13-acetate-sensitive protein kinase C did not block CD28- and CD3-induced tyrosine phosphorylation of Pyk2. These data provide evidence for the involvement of Pyk2 in the CD28 signaling cascade and suggest that neither Fak nor paxillin is involved in the signaling pathways of CD28.  (+info)

Interaction of B cells with activated T cells reduces the threshold for CD40-mediated B cell activation. (4/2090)

CD154-CD40 interactions are of central importance for the induction of antibody responses to T-dependent antigens. Since most anti-CD40 mAb are only weak B cell mitogens, it is believed that under physiological conditions, signals through CD40 synergize with those from other receptors on B cells to induce B cell activation. We show here that the interaction of either normal B cells, or those from CBA/N (xid) mice, with CD3-activated primary T cells in whole spleen cell cultures markedly reduces the threshold for B cell activation via CD40. Hence, these pre-activated cells undergo vigorous proliferation when stimulated with either optimal or suboptimal concentrations of weakly mitogenic anti-CD40 mAb, or with soluble CD40 ligand. Blocking experiments indicate that the establishment of this priming effect requires stimulation via CD40 itself, plus T cell-derived IL-2. In support of this concept, only CD3/CD28-pre-activated, but not CD3-pre-activated T cells induce this effect, unless the co-cultures of B cells with the latter T cells are supplemented with IL-2. Although B cells activated in this fashion do express higher levels of CD40 than naive cells, we believe that this is insufficient to explain the observed dramatic effects on their proliferative capacity. Rather we propose that T cell-dependent B cell activation induces fundamental changes in the signalling machinery invoked by ligation of CD40. It is likely that this amplification loop could play an important role during the initiation of antibody responses to T-dependent antigens, when activated CD4 T cells only express low levels of CD154.  (+info)

Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo. (5/2090)

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase-linked PI3K, p110delta, is characterized and its functional impact assessed. In vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta. Antisera specific for phospho-Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110delta that is recruited to activated receptors (such as CD28 in T cells) shows a time-dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039-phosphorylated p110delta. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110delta itself, are involved in the in vivo phosphorylation of p110delta. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules.  (+info)

Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28- cytotoxic effector clones. (6/2090)

CD8 T cells contain a distinct subset of CD8+ CD28- cells. These cells are not present at birth and their frequency increases with age. They frequently contain expanded clones using various TCRalphabeta receptors and these clones can represent >50% of all CD8 cells, specially in old subjects or patients with chronic viral infections such as HIV-1. Herein, it is shown that a large fraction of CD8+ CD28- cells expresses intracellular perforin by three-color flow cytometry, in particular when this subset is expanded. Together with their known ability to exert potent re-directed cytotoxicity, this indicates that CD8+ CD28- T cells comprise cytotoxic effector cells. With BrdU labeling, we show that CD8+ CD28- cells derive from CD8+ CD28+ precursors in vitro. In addition, sorted CD8+ CD28+ cells gave rise to a population of CD8+ CD28- cells after allo-stimulation. Moreover, ex vivo CD8+ CD28+ cells contain the majority of CD8 blasts, supporting the notion that they contain the proliferative precursors of CD8+ CD28- cells. CD95 (Fas) expression was lower in CD8+ CD28- cells, and this subset was less prone to spontaneous apoptosis in ex vivo samples and more resistant to activation-induced cell death induced by a superantigen in vitro. Thus, the persistence of expanded clones in vivo in the CD8+ CD28- subset may be explained by antigen-driven differentiation from CD8+ CD28+ memory precursors, with relative resistance to apoptosis as the clones become perforin(+) effector cells.  (+info)

The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases. (7/2090)

The proto-oncogene Cot/Tpl-2 encodes a MAP3K-related serine-threonine kinase. Expression of wild type Cot activates the IkappaB kinases (IKK) leading to induction of NF-kappaB. Conversely, expression of kinase-deficient Cot inhibits CD3/CD28 but not TNF alpha induction of NF-kappaB. These findings suggest the selective involvement of Cot/Tpl-2 or a closely related kinase in the CD3/CD28 costimulatory pathway leading to induced nuclear expression of NF-kappaB. In contrast, a kinase-deficient mutant of the NF-kappaB-inducing kinase (NIK) inhibits both CD3/CD28 and TNF alpha signaling, indicating that these pathways converge at or prior to the action of NIK. Consistent with such a sequential function of these two kinases, Cot physically assembles with and phosphorylates NIK in vivo.  (+info)

Cutting edge: alloimmune responses against major and minor histocompatibility antigens: distinct division kinetics and requirement for CD28 costimulation. (8/2090)

Comparative study of alloimmune responses against major and minor histocompatibility Ags has been limited by the lack of suitable assays. Here, we use a bioassay that permits tracking of alloreactive CD4+ T cell populations as they proliferate in response to major or minor histocompatibility Ags in vivo. Division of alloreactive CD4+ T cells proceeded more rapidly in response to major histocompatibility Ags than minor Ags, although CD4+ T cells alloreactive to minor Ags had a similar capacity to divide successively up to eight times after stimulation. Allorecognition of minor histocompatibility Ags was highly dependent on CD28 costimulation, with the frequency of CD4+ T cells proliferating in response to minor Ags in the absence of CD28 costimulation reduced up to 20-fold. These findings highlight differences in signaling processes that lead to allorecognition of major and minor histocompatibility Ags and have implications on the design of interventions aimed at abrogating these responses.  (+info)

TY - JOUR. T1 - Expression of the costimulatory receptor CD30 is regulated by both CD28 and cytokines. AU - Gilffillan, Molly C.. AU - Noel, Patricia J.. AU - Podack, Eckhard R.. AU - Reiner, Steven L.. AU - Thompson, Craig B.. PY - 1998/3/1. Y1 - 1998/3/1. N2 - Costimulation was originally defined and characterized during primary T cell activation. The signaling events that regulate subsequent antigen encounters by T cells are less well defined. In this study we examined the role of CD30 in T cell activation and defined factors that regulate expression of CD30 on T cells. We demonstrate that CD30 expression is restricted to activated T cells and regulated by CD28 signal transduction. In contrast to CD28-expressing TCR Tg cells, CD28-deficient TCR Tg cells did not express CD30 when cultured with peptide and APCs. However, rIL-4 reconstituted CD30 expression on CD28-deficient TCR Tg cells. Blockade of CD28 interactions or depletion of IL-4 inhibited the induction of CD30, suggesting that both ...
OX40 is really a T cell costimulatory molecule that belongs to the TNFR superfamily. exhausted Treg phenotype can be prevented by exogenous IL-2, as both OX40 and IL-2 agonists drive further expansion of Tregs in vivo. Importantly, Tregs expanded by both OX40 and IL-2 agonists are potent suppressor cells, and in a heart transplant model, they promote long-term allograft survival. Our data uncover a novel role for buy Bedaquiline (TMC-207) OX40 in buy Bedaquiline (TMC-207) promoting immune tolerance and may have important clinical implications. strong class=kwd-title Keywords: Costimulation, Transplantation, Tolerance, OX40, Foxp3 Introduction Foxp3+ Tregs and conventional T cells (Tconv) express a plethora of cell surface molecules including T cell costimulatory molecules that potentially influence their survival, function, and homeostasis; some of these molecules are constitutively expressed by both Tregs and Tconv (e.g., CD27, CD28, CD39), while others are preferentially expressed by Tregs, ...
During evolutionary adaptation in the immune system, host defense is traded off against autoreactivity. Signals through the costimulatory receptor CD28 enable T cells to respond specifically to pathogens, whereas those through the related costimulatory receptor, ICOS, which arose by gene duplication, are critical for affinity maturation and memory antibody responses. ICOS ligand, unlike the pathogen-inducible CD28 ligands, is widely and constitutively expressed in the immune system. Here, we show that crosstalk between these two pathways provides a mechanism for obviating the normal T cell dependence on CD28. Several CD28-mediated responses-generation of follicular helper T cells, germinal center formation, T helper 1 cell-dependent extrafollicular antibody responses to Salmonella and bacterial clearance, and regulatory T cell homeostasis-became independent of CD28 and dependent on ICOS when the E3 ubiquitin ligase Roquin was mutated. Mechanisms to functionally compartmentalize ICOS and CD28 signals are
Previous studies have demonstrated associations between the expression of the costimulatory receptor CD28 on CD8+ T cells (CD8+T cells with CD28- (null) expression/% of CD8+ T cells), but not on CD4+ T cells, with the defective humoral immune response (HAI titers) after influenza vaccination, Th1/Th2 cytokine disbalance and the development of immune deficiency in the elderly [6,7,8]. by searching the following DOI: 10.7303/syn3219180. Influenza Hemagglutinin (HA) Peptide Additional data from the cohort is available through NIHs ImmPort website ( Abstract Background Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development ...
Signaling mediated through the IL-2R, in conjunction with signals mediated through the T cell Ag receptor, promotes the proliferation and effector function of T cells (32). Some of the signals, such as up-regulation of the IL-2R α-chain, result from cooperative signals mediated both through the T cell Ag receptor as well as through the IL-2R itself; however, the relative role of signals delivered through these pathways has not been fully elucidated. Human tumor-reactive effector T cells have been shown to proliferate extensively in vitro in the presence of high-dose IL-2 alone (33). In addition, between 15 and 20% of melanoma and renal cancer patients treated with high-dose IL-2 alone respond to therapy (6), which may reflect the ability of IL-2 to maintain the proliferation of T cells that were activated by prior exposure to tumor Ags.. Interactions between the costimulatory receptor CD27 and its ligand, CD70, have also been found to play a key role in T lymphocyte activation, proliferation, ...
In addition to activation via the TCR complex, resting purified T cells can be activated to proliferate by mAb directed against the two surface molecules, CD2 and CD28. We demonstrate here that only the CD2 plus CD28 combined activation induces the expression and secretion of IL-1 alpha, a cytokine classically considered as a monokine. In contrast, neither IL-1 beta nor IL-6 were produced. A second monokine, TNF-alpha was transiently expressed by T cells activated with either CD2 or CD28 mAb, but was expressed to higher levels and with a prolonged kinetics in cells activated by the CD2 plus CD28 combination. The prolonged expression of the IL-1 alpha gene could account, at least in part, for the monocyte-independent and long lasting T cell proliferation induced by the CD2 plus CD28 co-stimulation. Secretion of monokines, such as IL-1 alpha, by activated T cells, could play a regulatory role in immune responses, as well as contribute to autoimmune processes. ...
The induction of survival versus apoptosis is a central issue during T cell development and activation. The differential regulation of thymocyte survival versus death through TCR-mediated selection signals plays a key role in establishing a functional mature T cell repertoire (1). In mature T cells, several studies have demonstrated that signals from MHC molecules are required for the survival of resting T cells (2)(3)(4). In addition, the induction of apoptosis is strictly regulated after antigenic triggering (5). However, during T cell activation, the T cell costimulatory molecule CD28 is believed to contribute to survival signals (6)(7)(8).. Several molecules have been identified that play key roles in regulating apoptosis in T cells (9). Important advances in understanding T cell apoptosis have come through the study of Bcl-2 family members. Bcl-2-related proteins function to promote either cell survival (such as Bcl-2 and Bcl-XL) or cell death (such as Bax and BAD). Several studies have ...
A population of individual T cells expressing an invariant V24JQ T cell antigen receptor (TCR) chain and high levels of CD161 (NKR-P1A) appears to play an immunoregulatory role through production of both T helper (Th) type 1 and Th2 cytokines. and cytokine secretion in response to CD1d+ target cells, demonstrating a physiological accessory molecule function for CD161. However, CD1d-restricted target cell lysis by activated V24invt T cells, which involved a granule-mediated exocytotic mechanism, was CD161-impartial. In further contrast to the mouse, the signaling pathway involved in V24invt T cell costimulation through CD161 did not appear to involve stable association with tyrosine kinase p56Lck. These results demonstrate a role for CD161 as a novel costimulatory molecule for TCR-mediated acknowledgement of CD1d by human V24invt T cells. (Camarillo, CA). Functional Analysis of T Cells. For activation of T cells (105/ well), anti-CD3 mAb OKT3 was bound overnight in PBS (50 l/well) to 96-well ...
The CD28 antibody is specific for the mouse CD28 costimulatory molecule, expressed on most thymocytes, CD4+ and CD8+ T cells, and natural killer (NK) cells. Ligation of CD28 with CD80 (B7-1) and CD86 (B7-2) provides a costimulatory signal for T cell activation. Clone 37.51 has been shown to activate T cells in combination with CD3. Activation and proliferation of T cells can be induced by interaction of the T cell receptor with peptide-MHC complexes. The T cell receives a signal transduced through the CD3 complex. Cytokines or other costimulatory signals from accessory cells are required in addition. Activated T cells can be used for any downstream processes, such as cytokine analysis or immunoprecipitation. Cells can also be transfected with high efficiency. - Italia
The CD28 antibody is specific for the mouse CD28 costimulatory molecule, expressed on most thymocytes, CD4+ and CD8+ T cells, and natural killer (NK) cells. Ligation of CD28 with CD80 (B7-1) and CD86 (B7-2) provides a costimulatory signal for T cell activation. Clone 37.51 has been shown to activate T cells in combination with CD3. Activation and proliferation of T cells can be induced by interaction of the T cell receptor with peptide-MHC complexes. The T cell receives a signal transduced through the CD3 complex. Cytokines or other costimulatory signals from accessory cells are required in addition. Activated T cells can be used for any downstream processes, such as cytokine analysis or immunoprecipitation. Cells can also be transfected with high efficiency. - España
APC anti-human Lineage Cocktail (CD3, CD14, CD16, CD19, CD20, CD56) - This anti-Human Lineage Cocktail is optimized for the detection of human peripheral blood T cells, B cells, NK cells, monocytes, and neutrophils.
B7-DC costimulates PD1−/− CD4+ T cells. (a) Purified CD4+ T cells from wt (open bars) or PD-1 KO mice (filled bars) were stimulated with 30 ng/well of preco
Methods and Results: High-purity sorted CD4+ T cells from ACS patients were treated with a panel of cytokines (TNF-α, IL-1β, IL-6, IL-7, IL-15), and effects on the number, phenotype and function of CD28null T cells were analysed and compared to the control counterpart CD28+ T cell subset. IL-7 and IL-15 induced expansion of CD28null T cells from ACS patients, while inflammatory cytokines TNF-α, IL-1β and IL-6 did not. The mechanisms underlying CD28null T cell expansion by IL-7/IL-15 were preferential activation and proliferation of CD28null T cells compared to control CD28+ T cells. Additionally, IL-7/IL-15 markedly augmented CD28null T cell cytotoxic function and interferon-γ production. Further mechanistic analyses revealed differences in baseline expression of component chains of IL-7/IL-15 receptors (CD127 and CD122) and increased baseline STAT5 phosphorylation in CD28null T cells from ACS patients compared to the control CD28+ T cell subset. Notably, we demonstrate that CD28null T cell ...
Costimulation is a fundamental principle of T-cell activation. In addition to T-cell receptor engagement, the interaction between CD80 and/or CD86 with CD28 and/or cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptors is required to regulate T-cell activation and tolerance. While the importance of costimulation is clearly established, the exact molecular mechanism is unknown. We demonstrate that T-cell proliferation and the ability of CD8(+) T-effector cells to kill were enhanced slightly by CD80 but dramatically by CD86 costimulation. To further analyse the cellular process of costimulation, we developed a single-cell assay to analyse Ca(2+) signals following costimulation with bi-specific antibodies. We found that this stimulation method worked in every human T-cell that was analysed, making it one of the most efficient T-cell activation methods to date for primary human T cells. The enhanced proliferation and killing by costimulation was paralleled by an increase of Ca(2+) influx following CD86 ...
Dr. Allisons pioneer work has transformed the fields of basic and tumour immunology. Early in his career, he identified and characterized key molecules involved in T-cell activation, including the T-cell receptor (TCR), the prototypical costimulatory receptor CD28 and coinhibitory receptor CTLA-4, providing evidence that T-cell responses are determined by a complex process involving antigen driven TCR signalling plus integration of costimulatory and coinhbitory signals. His landmark translation studies showing antibody-mediated blockade of CTLA-4 co-inhibitory function could enhance antitumor immunity and result in tumour rejection in mice prompted clinical development of ipilimumab, a CTLA-4 blocking monoclonal antibody. Ipilimumab is the first drug of its kind to show survival benefit in melanoma patients and was approved by the FDA in 2011 as a standard-of-care therapy for late-stage melanoma patients. Dr. Allisons concept of antibody-mediated blockade of immunologic checkpoints as cancer ...
Therapeutic tumor immunity requires the presence and appropriate activation of tumor antigen specific CD8+ T cells and migration of activated tumor-antigen specific CD8+ T cells into a tumor microenvironment where immunosuppressive barriers have been eliminated. Antibody mediated blockade of CTLA-4 and PD-1 is a clinically effective strategy to dampen tumor mediated immunosuppression in a minority of patients with advanced cancer, and this approach may be potentiated through vaccination to prime additional CTL clones and through direct stimulation of T cell costimulatory molecules of the TNF superfamily. Here we provide a systematic comparison of anti-tumor vaccination with either heat shock protein gp96-Ig or traditional peptide/adjuvant vaccines given alone or in combination with CTLA-4 or PD-1 blockade and direct T cell costimulation via OX40, 4-1BB and TNFRSF25. Through the tracking of tumor-antigen specific CD4+ and CD8+ T cell responses, these studies demonstrate that both TNFRSF4 and ...
These observations suggest that the susceptibility of CD3/CD28-stimulated cells to TCL-tropic viruses results from up-regulation of CXCR-4/Fusin mRNA expression, consistent with the high level of fusion between CD3/CD28-stimulated cells and cells expressing TCL-tropic envelope glycoproteins. Furthermore, the resistance of CD3/CD28-activated cells to infection by M-tropic viruses and primary isolates of HIV-1 correlates with the absence of detectable CCR5 mRNA expression. This result is consistent with the inability of CD3/CD28-stimulated cells to fuse with cells expressing M-tropic envelope glycoproteins.. Although the mechanism by which CCR5 expression is inhibited in CD3/CD28-stimulated CD4+ cells is unknown, CD28 costimulation exerts many effects on gene expression in general and cytokine expression in particular (3, 12). CD28-induced down-regulation of β-chemokine receptors may be a general feature in T cells, as Loetscher and colleagues recently reported that costimulation of CD4+ cells ...
To study the signaling role of CD11a/CD18 in the early events of T cell activation we have examined the induction of transcription of two important cytokines, namely TNF alpha and IL-2. Human peripheral blood T cells were stimulated with PMA/ionophore or immobilized anti-CD3 mAb (OKT3) with or without CD11a/CD18 engagement. Induced cytokine production by immobilized OKT3 was enhanced (3- to 10-fold) in cells adhering to OKT3 and ICAM-1 coimmobilized surfaces and anti-CD11a mAb abolished this enhancement effect. Similarly, inhibition of the PMA/ionophore-induced CD11a/CD18-mediated homotypic aggregations of T cells by mAbs specific for either CD11a or ICAM-1 reduced the induced cytokine production by more than 70%. We have also observed that greatly enhanced cytokine production resulted from cellular interactions between activated T cells and monolayers of endothelial cells. This enhancement was inhibited by a combination of CD11a-, CD18-, and ICAM-1-specific mAbs implicating a role of CD11a/CD18 ...
|span style=font-family:Times,serif;font-size:9pt;>The MR1 monoclonal antibody specifically binds to CD154 (CD40 Ligand, gp39), an accessory molecule expressed on activated T helper (CD4+) lymphocytes. CD154 has also been detected on other types of leukocytes, including CD8+ T cells, medullary thymocytes, activated CD4+ NK-T cells, and human NK cells. CD154 plays an important role in costimulatory interactions between T and B lymphocytes and between antigen-presenting cells and lymphocytes, regulating the immune response at multiple levels. MR1 mAb inhibits in vitro activation of B lymphocytes by T helper cells by blocking interaction of gp39 with CD40. |/span>|span style=font-style:italic;font-family:Times,serif;font-size:9pt;>In vitro |/span>|span style=font-family:Times,serif;font-size:9pt;>interactions of T cells and antigen-presenting cells can also be blocked by the MR1 antibody. |/span>|span style=font-style:italic;font-family:Times,serif;font-size:9pt;>In vivo|/span>|span style=font
T cell activation through the TCR can result in either cell proliferation or cell death. The role of costimulatory receptors in regulating T cell survival has not been defined. Here, we present data demonstrating that CD28 costimulation enhances the in vitro survival of activated T cells. One mechan …
The 2 signal model provides the framework for our understanding of T cell responses. Using high throughput microarray analysis we have uncovered several novel TCR-induced genes and pathways that play critical roles in dictating the outcome of antigen recognition. We identified Egr-2 and Egr-3 as playing an important role in determining the fate of TCR recognition (Signal 1). Egr-2 and Egr-3 null T cells induce more aggressive autoimmune disease but are more effective in mounting anti-tumor responses. A second gene that was revealed by our screen is the adenosine A2aR. Activating the receptor can promote tolerance and inhibit autoimmune disease. Alternatively employing A2aR null mice and specific antagonists promotes anti-tumor immunity and enhances vaccine responses. In addition to Signal 1, we are also interested in understanding mechanisms of costimulation. Along these lines we have identified the mammalian Target of Rapamycin (mTOR) as playing a central role in dictating the outcome of ...
We have shown that a KIR-CAR can be simply constructed by swapping the two immunoglobulin-like domains of the KIR2DS2 ectodomain with an scFv capable of binding a desired target antigen. When delivered to T cells together with DAP12, this KIR-based CAR triggers antigen-specific cytotoxicity, cytokine production, and proliferation that is comparable with second-generation CD3ζ-based CARs in vitro without the need for additional domains from costimulatory receptors. The ability of a KIR-based CAR to activate T cells in the absence of added costimulation is interesting in light of the critical importance of costimulation for full T-cell activation and acquisition of effector function. KIR2DS2, the natural KIR upon which the presented KIR-CAR is based, has previously been reported to deliver a costimulation-like signal to T cells. In these studies, engagement of the KIR in T-cell clones lacking DAP12 expression augmented anti-CD3-induced IFNγ production (16). The mechanism of this costimulatory ...
Changes of CD8/HLADR+ T cells during a period of seven years HAART ( ± SD,/ μL). Patient numbers: Effective group (A) (n = 25), Ineffective group (B) (n = 18)
Bovine TSH (bTSH) has a higher affinity to the human TSHR (hTSHR) and a higher signaling activity than human TSH (hTSH). The molecular reasons for these phenomena are unknown. Distinct negatively charged residues (Glu297, Glu303, and Asp382) in the hinge region of the hTSHR are known to be important …
|span style=font-family:Times,serif;color:#000000;font-size:9pt;>The GL1 antibody specifically recognizes the B7-2 (CD86) costimulatory molecule expressed on a broad spectrum of leukocytes, including B lymphocytes, T lymphocytes, thioglycollate-induced peritoneal macrophages, dendritic cells and astrocytes. CD86 is expressed at low levels by freshly explanted peripheral B and T cells, and its expression is substantially increased by a variety of T cell- and B cell-specific stimuli with a peak expression after 18-42 hours of culture. In contrast to most naive CD4+ T cells, memory CD4+ T cells express B7-2, both at the mRNA and protein level. CD86, a ligand for CD28 and CD152 (CTLA-4), is one of the accessory molecules that plays an important role in T cell-B cell costimulatory interactions. It has been shown to be involved in immunoglobulin class-switching and triggering of mouse NK cell-mediated cytotoxicity. CD80 (B7-1) is an alternate ligand for CD28 and CD152 (CTLA-4). GL1 antibody reportedly
Signaling through CD27 plays a role in T cell activation and memory. However, it is currently unknown how this costimulatory receptor influences CD4 effector T (Teff) cells in inflamed tissues. In the current study, we used a murine model of inducible self-antigen expression in the epidermis to elucidate the functional role of CD27 on autoreactive Teff cells. Expression of CD27 on Ag-specific Teff cells resulted in enhanced skin inflammation when compared with CD27-deficient Teff cells. CD27 signaling promoted the accumulation of IFN-γ and IL-2-producing T cells in skin draining lymph nodes in a cell-intrinsic fashion. Surprisingly, this costimulatory pathway had minimal effect on early T cell activation and proliferation. Instead, signaling through CD27 resulted in the progressive survival of Teff cells during the autoimmune response. Using BH3 profiling to assess mitochondrial cell priming, we found that CD27-deficient cells were equally as sensitive as CD27-sufficient cells to mitochondrial ...
Methods: T cells were activated with anti-CD3/28 antibodies and subsequently transduced with a bicistronic retrovirus encoding tandem Rim-binding domains (FKBP12v36),cloned in-frame with MyD88 and CD40 cytoplasmic signaling molecules, and first generation CAR targeting CD123 (SFG-iMC-CD123.ζ). The effects ofiMC costimulation on CD123-targeted CARs were assessed in coculture assays with CD123+, EGFPluciferase (EGFPluc)-modified leukemic cell lines (KG1, THP-1 and MOLM-13) with and without Rim using the IncuCyte live cell imaging system. IL-2 production was examined by ELISA from coculture supernatants. In vivo efficacy of iMC-CD123.ζ-modified T cells was assessed using an immune-deficient NSG tumor xenograft model. One million EGFPluc-expressing CD123+ THP-1 tumor cells were injected i.v. into the animals, followed by a single i.v. injection on day 7 with 2.5x106 non-transduced or iMC-CD123.ζ-modified T cells. Groups receiving CAR-T cells subsequently received i.p. injections of Rim (1 mg/kg) ...
In mammals, the classical B7 molecules expressed on antigen-presenting cells, B7-1 (CD80) and B7-2 (CD86), bind the structurally related glycoproteins CD28 and CTLA-4 (CD152), generating costimulatory signals that regulate the activation state of T cells. A recently identified human CD28-like protein, ICOS, also induces costimulatory signals in T cells when crosslinked with antibodies, but it is unclear whether ICOS is part of a B7-mediated regulatory pathway of previously unsuspected complexity, or whether it functions independently and in parallel. Here, we report that, rather than binding B7-1 or B7-2, ICOS binds a new B7-related molecule of previously unknown function that we call LICOS (for ligand of ICOS). At 37 degrees C, LICOS binds only to ICOS but, at lower, non-physiological temperatures, it also binds weakly to CD28 and CTLA-4. Sequence comparisons suggest that LICOS is the homologue of a molecule expressed by avian macrophages and of a murine protein whose expression is induced in non
Altor is building on our IL-15 technology to create a next-generation targeted IL-15 scaffold platform to recognize and target specific antigens found in various cancers and viral infections. We have adapted the IL-15 superagonist complex to create a functional scaffold for the design of multi-specific fusion protein complexes. Using an antibody or single-chain T cell receptors (STARTM) as recognition domains linked to the IL-15 scaffold, we have generated both bivalent and bispecific product candidates (TxM).. Extensive characterization of these product candidates consisting of therapeutic antibodies and this scaffold indicates that such a targeted immunotherapeutic can potentiate the anti-tumor activities of the therapeutic antibody as well as potently facilitate immune responses. Thus, we are utilizing this IL-15 scaffold platform to generate multiple targeted IL-15 product candidates that can simultaneously promote killing of target cells and retain immunostimulatory functions of ...
We next determined the function of the CD4+CD25+ T cells. For these experiments we used the CD4+CD25- and CD4+CD25+ peripheral blood T cells whose FoxP3 expression levels were shown in Figure 1 (a and b). These T cell subsets were assessed for their ability to respond to T cell receptor (TCR) stimulation, and for the ability of the CD25+ cells to suppress the in vitro activation of the CD25- cells. When cultured in the presence of feeder cells along with soluble anti-CD3 and anti-CD28, the CD4+CD25- cells responded with robust proliferation, whereas the CD4+CD25+ cells did not (Figure 1c). When the two populations were cocultured, the level of proliferation, as measured by 3H-thymidine incorporation, was dramatically reduced (Figure 1c). The level of suppression seen was correlated with the ratio of CD4+CD25-:CD4+CD25+ cells in the culture, with more CD25+ cells resulting in more suppression of CD25- cell proliferation. These results are not due to exhaustion of the resources within the culture ...
The modulation of co-stimulatory pathways represents a novel therapeutic strategy to regulate autoimmune diseases. Auto-reactive CD4+ T cells play a critical role in initiating the immune response leading to inflammation and autoimmune diseases. Blocking co-stimulatory signals prevents T-cell activation, thus diminishing autoimmune responses and possibly preventing the progression of autoimmune disease. Blockade of several co-stimulatory pathways has been investigated in animal models and has led to clinical trials testing specific blocking agents in humans. In this review we will describe the role of co-stimulatory pathways, primarily the CD28-B7 pathway, in autoimmune diseases, and we will present in vivo and in vitro studies supporting the efficacy of co-stimulation blockade in animal models of autoimmune disease. Finally, we will discuss the clinical therapeutic efficacy of blocking monoclonal antibodies in preventing or reducing auto-antigen driven T-cell activation in humans with ...
This dissertation focuses on the hypothesis that simultaneous blockade of multiple costimulatory pathways involved in T cell activation prolongs allograft survival and alters cell-mediated immunity. Two independent but necessary costimulatory pathways, the CD2 and CD28/CTLA4 coreceptors, were blocked using anti-CD2 monoclonal antibody and the fusion protein CTLA4Ig. Previous work has shown the importance ofCD2 in T cell activation and the immunosuppressive effects of anti-CD2 monoclonal antibody. The work presented here explored the immunosuppressive effects of CTLA4Ig. U sing a heterotopic nonvascularized cardiac allograft model and model of cell mediated immunity, CTLA4Ig was shown to be a potent immunosuppressant at the time of antigen presentation, prolonging allograft survival and inhibiting cell mediated immunity by altering both CD4+ and CD8+ T cell responses. Combining anti-CD2 monoclonal antibody with CTLA4Ig at the time of antigen presentation is a more immunosuppressive regimen, as ...
To our knowledge, expression of B7-H1 within RCC tumors of the kidney has not been previously demonstrated. We also believe that B7-H1 is the first T cell costimulatory molecule that has been reported to exhibit a strong association with the aggressiveness of a solid (nonhematologic) tumor and patient cancer-specific survival. Finally, our study provides previously undescribed evidence that B7-H1 may function at the clinical level to promote cancer progression, perhaps through impairment of host T cell-mediated immunity, as has recently been reported in the basic scientific literature (2, 6).. B7-H1 represents a recently identified cell-surface glycoprotein belonging to the B7 family of costimulatory molecules (1). Constitutive B7-H1 protein expression is normally restricted to macrophage-lineage cells, where it may participate in the costimulatory activation of naïve T cells or deletion of activated T cells (1, 23). Several human cancers, however, have also been reported to aberrantly express ...
Treatment of advanced, poorly immunogenic tumors in animal models, considered the closest simulation available thus far for conditions observed in cancer patients, remains a major challenge for cancer immunotherapy. We reported previously that established tumors in mice receiving an agonistic mAb to the T cell costimulatory molecule 4-1BB (CD137) regress due to enhanced tumor antigen-specific cytotoxic T lymphocyte responses. In this study, we demonstrate that several poorly immunogenic tumors, including C3 tumor, TC-1 lung carcinoma, and B16-F10 melanoma, once established as solid tumors or metastases, are refractory to treatment by anti-4-1BB mAb. We provide evidence that immunological ignorance, rather than anergy or deletion, of tumor antigen-specific CTLs during the progressive growth of tumors prevents costimulation by anti-4-1BB mAb. Breaking CTL ignorance by immunization with a tumor antigen-derived peptide, although insufficient to stimulate a curative CTL response, is necessary for ...
CD26, also known as dipeptidyl peptidase IV (DPP-IV), is a homodimeric cell surface serine peptidase that degradates IFN-gamma-induced cytokines, acts as a T cell costimulatory molecule, and participates in multiple immunopathological roles in leukocyte homing and inflammation. Alterations in its peptidase activity are characteristic of malignant transformation. The enzymatic activity increases dramatically with tumour grade and severity. CD26 is expressed in various blood cell types, but also e.g. in cells that are histogenetically related to activated fibroblasts. Alterations in CD26 density have been reported on circulating monocytes and CD4+ T cells during rheumatoid arthritis and systemic lupus erythematosus ...
Interleukin-2 (IL-2) stimulates both activated CD4+ and CD8+ T cells to proliferate. IL-2 signals through an identical receptor complex and promotes the same dose-dependent phosphorylation of the canonical transcription factor STAT5 in both cell types. Despite this, CD8+ T cells enter the S phase earlier and proliferate to a greater extent than do CD4+ T cells in response to IL-2. We identified distinct IL-2 signaling dynamics in CD4+ and CD8+ T cells. In IL-2-stimulated CD8+ T cells, STAT5 phosphorylation increased rapidly and was sustained for 6 hours. In contrast, CD4+ T cells had a biphasic response, with maxima at 15 min and 2 to 4 hours after stimulation. Both cell types required vesicular trafficking, but only CD4+ T cells required new protein synthesis to maintain high phosphorylation of STAT5. Two subunits of the IL-2 receptor, IL-2Rβ and IL-2Rγ, were twice as abundant in CD8+ T cells than in CD4+ T cells. Reduction of IL-2Rβ abundance by 50% was sufficient to convert CD8+ T cells to ...
Protein Kinase C Theta Type (nPKC Theta or PRKCQ or EC - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at
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doi:10.1371/journal.pone.0076104. an infection. Hence, the VX-765 (Belnacasan) activation of NK cells, essential mediators from the innate immune system response, by treatment with an IL-15 superagonist boosts their anti-HIV activity and allows these to potently suppress severe HIV-1 an infection. These results indicate that activation of NK cells might represent a fresh immunotherapeutic method of suppress severe HIV-1 infection. IMPORTANCE Epidemiological research have got indicated that NK cells donate to the control of HIV-1 an infection, and research have got demonstrated that NK cells may wipe out HIV-1-infected cells selectively. We showed that activation of NK cells by treatment with an IL-15 superagonist that potently stimulates the antitumor activity of NK cells markedly inhibited severe HIV-1 an infection in humanized mice, even though activation of NK cells by IL-15 superagonist treatment is normally postponed until 3 times after HIV-1 inoculation. NK cell depletion from PBMCs ahead ...
The present results verify the previously suggested, but not definitively proven, mechanism that α-GalCer-activated iNKT-cells at least partly protect NOD mice from type 1 diabetes by driving the maturation of tolerogenic DCs. In contrast, iNKT-conditioned DCs in B6.H2g7 mice mature to an alternative immunogenic state that supports rather than inhibits AI4 T-cell-induced type 1 diabetes. The downstream maturation of iNKT-conditioned DCs in NOD and B6.H2g7 mice to a tolerogenic versus an immunogenic state is due to the induction of quantitatively different expression levels of T-cell costimulatory and inhibitory molecules.. A series of T-cell costimulatory molecules were upregulated to a much greater extent on iNKT-conditioned DCs from B6.H2g7 than NOD mice. In particular, CD70 and OX40L expression levels were unchanged or strongly upregulated on iNKT-conditioned DCs from NOD and B6.H2g7 mice, respectively. This could be significant given a report that iNKT-cells promote CD8+ cytotoxic T-cell ...
CD152 (CTLA-4), PE, clone: 14D3, eBioscience™ 25 Tests; PE CD152 (CTLA-4), PE, clone: 14D3, eBioscience™ Primary Antibodies CD151 to CD200
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Del Guercio. 1905[1904]. Sulle differenze esistenti fra la Schizoneura Reaumuri Kalt. ed il Pachypappa vesicalis Koch e sulla convenienza di escludere la prima dal genere per essa indicate. Redia 2(2):306 ...
Given the opposing negative effect of CTLA-4 on T cell activation (4, 5), we next assessed whether CTLA-4 coligation could alter the surface expression of rafts. Coligation of CTLA-4 with either TcR, or the combination of TcR and CD28 potently inhibited GM1 expression (Fig. 1 A). On average, CTLA-4 inhibited the percentage of GM1-positive cells by 70-90% so that the level of expression at 48-96 h exceeded that of the resting population by only 5-10%. CTLA-4 also inhibited the expression level on cells that had been induced to express GM1 as a result of anti-CD3 or anti-CD3/CD28 ligation (i.e., MIF of positively gated cells), albeit to a much lesser extent (i.e., MFI: 48 h: anti-CD3 versus anti-CD3/CTLA-4: 12.1 [61%] to 11.0 [55%]; anti-CD3/CD28 versus anti-CD3/CD28/CTLA-4: 13.6 [69%] to 11.9 [60%]). Inhibition of GM1 expression correlated with the anti-CTLA-4 blockage of proliferation (Fig. 1 B), and CD25 expression (Fig. 1 C). Our findings therefore show that CD28 and CTLA-4 have striking ...
CD4+CD28null T cells are a population of lymphocytes rarely found in healthy individuals.1,3 Although cell numbers increase with age, disease-associated expansions, in addition to ACS, have also been reported in inflammatory disorders such as rheumatoid vasculitis.18 The present study has addressed a critical point concerning antigen specificity and found that hHSP60 was recognized by CD4+CD28null cells via the MHC class II presentation pathway in ,50% of our patients with ACS. This finding is of significance because of the frequency and damaging potential of CD4+CD28null cells and the almost ubiquitous expression of HSPs.. The association between HSPs and atherosclerosis has been a subject of recent interest.7 The elevated expression of these proteins in atheromatous lesions, correlating with the severity of atherosclerosis, is consistent with a focal role that HSPs may play in the pathogenesis of the disease.19,20 This, combined with a growing body of evidence that suggests that risk factors ...
Adoptive transfer of CD4+CD25+ T cells inhibits HSV-1-specific CD8+ T cell responses. Purified CD4+CD25+ and CD4+CD25− T cells (2 × 106/mouse) were adoptively transferred into WT B6 mice 24 h before HSV infection, and the immune response was measured on days 7 and 28 p.i. (A) On days 7 and 28 p.i., spleen cells were incubated with gB498-505, and CD8/IFN-γ production was measured by intracellular staining. The number shown in each plot is the mean percentage of IFN-γ-producing CD8+ T cells obtained from four mice per group. (B) The resulting decrease in IFN-γ-secreting CD8+ T cells in B6 mice after adoptive transfer of CD4+CD25+ T cells were also measured by a standard ELISPOT assay. On days 7 and 28 post HSV infection, spleen cells were analyzed for the number of IFN-γ-secreting CD8+ T cells in response to SSIEFARL peptide. The error bars represent the mean ± SD of four different mice in the same group. *P , 0.05 compared with HSV-infected B6 mice receiving no adoptive transfer. Without ...
Asthma affects approximately 300 million people worldwide and is the most common chronic lung disease, which usually is associated with bronchial inflammation. Most research has focused upon the role of CD4+ T cells and relatively few studies have addressed the phenotypic and functional roles of CD8+ T cell types and subtypes.Human NK-like CD8+ T cells may involve cells that have been described as CD8+CD28-, CD8+CD28-CD57+, CD8+CD27-, or CD8+ effector-memory (TEM) cells, among other. However, most of the data which is available regarding these various cell types were obtained in murine models, did not thoroughly characterize these cells with phenotypically or functionally or did not involve asthma-related settings.Nevertheless, one may conceptualize three principal roles for human NK-like CD8+ T cells in asthma: disease-promoting, regulatory and/or tissue repair. Although evidence for some of these roles is scarce, it is possible to extrapolate some data from overlapping or related CD8+ T cell
TLR ligands act directly upon T cells to restore proliferation in the absence of protein kinase C-theta signaling and promote autoimmune ...
OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS: CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. RESULTS: The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] ...
Human mucosal associated invariant T (MAIT) CD8 + and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 ( ++) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17CD161 ++CD8αβ + T cells exist in cord blood, from which a prominent MAIT cell(TCR Vα7.2 +) population emerges postnatally. During this expansion, CD8αα T cells appear exclusively within aCD161 ++CD8 +/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161 ++CD8αβ + counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161 ++CD8 +T-cell pool and the distinct phenotype and function of CD8αα cells in man. © 2012 by The American Society of Hematology.
In the Research Article A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent, the right panel graph of Fig. 5D (siNRP1) was erroneously duplicated in the left panel (siCtl). However, correct experimental values were reported in table S4 (provided as an Excel file) that contains raw data relating to both siCtl and siNRP1 panels of Fig. 5D. The left panel of Fig. 5D has been replaced so that it now contains a graph plotted with correct siCtl values, as originally displayed in table S4. This error does not change the findings or conclusions of the study. The PDFs and HTML (full text) have been corrected.. ...
Interleukin (IL)-4 is considered to be essential for T helper (Th)2 cell development, yet in areas of primary T cell activation, CD4+ cells are its only source. This implies that other signals must drive the initial expression of IL-4 production. The role of CD28 co-stimulation in Th2 subset development has been described. However, in mice deficient for CD28, Th2 responses are diminished, but not abrogated. Cytokines produced within the lymphoid tissue, e.g. IL-7, may be important in the primary activation of naive CD4+ cells. We have found that human naive CD4+ cells purified from umbilical cord blood express the IL-7 receptor and respond vigorously to IL-7 during primary stimulation. Naive CD4+ cells grown in IL-4, in the presence or absence of IL-2, fail to produce Th2 cytokines upon restimulation. In contrast, IL-7 induces development of a population of T cells that produce large amounts of IL-4. Growth in IL-7 also increases IL-2-induced production of interferon (IFN)-gamma and IL-10 production. IL
The mechanism through which CD28 costimulation potentiates TCR-driven gene expression is still not clearly defined. Vav-1, an exchange factor for Rho GTPases thought to regulate, mainly through Rac-1, various signaling components leading to cytokine gene expression, is tyrosine phosphorylated upon CD28 engagement. Here, we provide evidence for a key role of Vav-1 in CD28-mediated signaling. Overexpression of Vav-1 in Jurkat cells in combination with CD28 ligation strongly reduced the concentration of staphylococcus enterotoxin E/MHC required for TCR-induced NF-AT activation. Surprisingly, upon Vav-1 overexpression CD28 ligation sufficed to activate NF-AT in the absence of TCR engagement. This effect was not mediated by overexpression of ZAP-70 nor of SLP-76 but necessitated the intracellular tail of CD28, the intactness of the TCR-proximal signaling cascade, the Src-homology domain 2 (SH2) domain of Vav-1, and SLP-76 phosphorylation, an event which was favored by Vav-1 itself. Cells overexpressing Vav-1
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Sino biological offers a comprehensive set of tools for CD antigens related to cell activation research, including recombinant proteins, antibodies,and others. This page about the CD antigens that expressed on T cells.
CD278 (ICOS), PE-Cyanine5, clone: C398.4A, eBioscience™ 50μg; PE-Cyanine5 CD278 (ICOS), PE-Cyanine5, clone: C398.4A, eBioscience™ Primary Antibodies...
CD4+ T cells play a major role in adaptive immune responses to intracellular and extracellular microbes by regulating the functions of B cells, CD8+ T cells, an...
In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM-1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co-engagement ...
CD3 epsilon兔单克隆抗体[E272](ab32186)可与人样本反应并经IP, IHC, ICC实验严格验证,被3篇文献引用。所有产品均提供质保服务,中国75%以上现货。
CD14兔多克隆抗体(ab106285)可与人样本反应并经WB, ELISA, IHC实验严格验证并得到1个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold ... is also not expressed on resting antigen presenting cells, but is following their activation. ... unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation ...
These proteins are expressed on the surface of antigen-presenting cells and interact with ligands (e.g., CD28; MIM 186760) on T ...
CD28 plays an important role in decreasing the risk of T cell auto-immunity against host antigens.[citation needed] Once the ... For example, when an antigen-presenting cell displays a peptide antigen on MHC class II proteins, a CD4+ cell will aid those ... During an immune response, professional antigen-presenting cells (APCs) endocytose antigens (typically bacteria or viruses), ... these T cells must rely on the activation of CD28 for confirmation that they recognise a foreign antigen (as CD80/CD86 is only ...
... or human CD28 identified so-called "superagonistic" antibodies that could stimulate T cells without concurrent antigen-receptor ... the CD28 receptor of the immune system's T cells. CD28 is the co-receptor for the T cell receptor; It binds to receptors on the ... "TGN1412 is a humanised monoclonal antibody directed against the human CD28 antigen. The molecule was genetically engineered by ... lack CD28 expression. Since CD28 is the target of the TGN1412 antibody, M. fascicularis effector T-cells could not be ...
"Inhibitory Role for Dual Specificity Phosphatase VHR in T Cell Antigen Receptor and CD28-induced Erk and Jnk Activation". ...
The interaction between CD86 (CD80) expressed on the surface of an antigen-presenting cell with CD28 on the surface of a mature ... Both CD80 and CD86 bind CTLA-4 with higher affinity than CD28. This allows CTLA-4 to outcompete CD28 for CD80/CD86 binding. ... To become activated, lymphocyte must engage both antigen and costimulatory ligand on the same antigen-presenting cell. T cell ... cytotoxic T-lymphocyte antigen-4, also known as CD152). CD28 and CTLA-4 have important, but opposite roles in the stimulation ...
Hombach, AA; Rappl, G; Abken, H (December 2013). "Arming cytokine-induced killer cells with chimeric antigen receptors: CD28 ... redirected by chimeric antigen receptors with an antibody-defined specificity for different tumor antigens, showed an improved ... The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ ... which can be exploited in combination with clinical-grade mAbs to redirect their activity in an antigen-specific manner. Indeed ...
... which can prevent an immune response to self-antigen. In addition to interactions with CD28 and CTLA-4, CD80 is also thought to ... CD80 binds to CD28 and CTLA-4 with lower affinity and fast binding kinetics (Kd =4 μM), allowing for quick interactions between ... van der Merwe PA, Bodian DL, Daenke S, Linsley P, Davis SJ (February 1997). "CD80 (B7-1) binds both CD28 and CTLA-4 with a low ... If the interaction between an antigen-presenting cell and a T-cell is stable enough, the T-cell can remove the CD80 from the ...
C3aR signaling along antigen-presenting cells' CD28 and CD40L pathways also plays a role in T cell proliferation and ... There are three pathways of activation, each of which leads to the formation of C3a and C3b, which is involved in antigen ... recognize and bind to pathogen-associated molecular patterns on the antigen, including sugars. These bound receptors then ...
"The CD28/B7 pathway costimulates the response of primary murine T cells to superantigens as well as to conventional antigens". ... Rockefeller University News, June 16, 1996 Blankson, J.; Loh, D.; Morse, S. (1995). "Superantigens and conventional antigens ... antigens in HIV-1-infected patients with immune reconstitution". The Journal of Infectious Diseases. 183 (4): 657-661. doi: ...
... these T cells must rely on the activation of CD28 for confirmation that they recognise a foreign antigen (as CD80/CD86 is only ... For example, when an antigen-presenting cell expresses an antigen on MHC class II, a CD4+ cell will aid those cells through a ... that a host antigen is foreign. As a result, the CD8+ T cells treat the host cell presenting that antigen as infected, and go ... but unprocessed antigens do not interact with T cells and are not involved in their activation. The antigens that bind to MHC ...
Another two stimulatory checkpoint molecules belongs to the B7-CD28 superfamily-CD28 itself and ICOS. CD27: This molecule ... The ligand for GITR is mainly expressed on antigen presenting cells. Antibodies to GITR have been shown to promote an anti- ... CD28: This molecule is constitutively expressed on almost all human CD4+ T cells and on around half of all CD8 T cells. Binding ... CD28 was the target of the TGN1412 'superagonist' which caused severe inflammatory reactions in the first-in-man study in ...
At the same time it has to ignore any self-antigen and tolerate harmless antigens such as food antigens. The signal ... It is not known that PI-3K is activated by the T cell receptor itself, but there is evidence that CD28, a co-stimulatory ... The antigen sensitivity is higher in antigen-experienced T cells than in naive T cells. Naive T cells pass through the process ... Also, the decision whether a T cell response to an antigen is made quickly. T cells rapidly scan pMHC on an antigen presenting ...
Role in T-lymphocyte activation". Tissue Antigens. 50 (5): 439-48. doi:10.1111/j.1399-0039.1997.tb02898.x. PMID 9389317. Soares ... "Ligation of the V7 molecule on T cells blocks anergy induction through a CD28-independent mechanism". J. Immunol. 159 (3): 1115 ...
PKC-θ is important in the signal pathway integrating signals from TCR and CD28 receptors. A junction between an APC (an antigen ... As a result of co-stimulation by CD28 and TCR, PKC-θ is sumoylated by SUMO1 predominantly on the sites Lys325 and Lys506. ... Takeda K, Harada Y, Watanabe R, Inutake Y, Ogawa S, Onuki K, Kagaya S, Tanabe K, Kishimoto H, Abe R (December 2008). "CD28 ... "Vav synergizes with protein kinase C theta to mediate IL-4 gene expression in response to CD28 costimulation in T cells". J. ...
... a costimulatory signal is transmitted by the interaction between CD28 and B7 of the precursor cell and the licensed antigen- ... In the second phase, affector CTLs destroy target cells by recognizing the antigen-MHC class I complex. In phase one, effector ... This results in proliferation and differentiation of the antigen-activated precursor cell into a functional effector CTL. In ... This step allows the cell to become licensed to an antigen-presenting cell. Second, ...
"Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 ... These antigens are recognized by dendritic cells that present the antigens to cytotoxic T lymphocytes (CTLs) in the lymph nodes ... Following the 1987 cloning of CTLA-4 in mice, its conservation in humans and similarities with CD28 were soon noticed. CD28 at ... The CTLs recognize the cancer cells by those antigens and destroy them. However, along with the antigens, the dendritic cells ...
Antigen-naive T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... Other receptors are expressed upon activation of the T cell, such as OX40 and ICOS, but these largely depend upon CD28 for ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help. Antigen ... These self-antigens are expressed by thymic cortical epithelial cells on MHC molecules on the surface of cortical epithelial ...
17%); pPCL plasma cells often lack CD56 antigen which is present on the majority of plasma cells taken form multiple myeloma ... patients; and pPCL plasma cells more frequently express CD28 than do sPCL plasma cells. Thus, immunophenotyping supports that ... For example: pPCL plasma cells more often express CD20 antigen, which is considered important in anchoring plasma cells to the ... Examination of plasma cell immunophenotype by measuring certain of their cell surface antigens, particularly Cluster of ...
NFkB is translocated to the nucleus after costimulation through CD28. NFkB is a heterodimer and there are two binding sites on ... One of the checkpoints is signaling through TCR, antigen receptor of T-lymphocytes after recognizing MHC-peptide complex. ... PLC activates 3 major transcription factors and their pathways: NFAT, NFkB and AP-1. After costimulation from CD28 the optimal ... which depends upon the expansion of the number and function of antigen-selected T cell clones, it plays a key role in enduring ...
... medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28 ... medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28 ...
... on antigen-presenting cells. CTLA-4 binds CD80 and CD86 with greater affinity and avidity than CD28 thus enabling it to ... It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. The CTLA-4 protein is encoded ... CTLA4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and ... T cell activation through the T cell receptor and CD28 leads to increased expression of CTLA-4. The mechanism by which CTLA-4 ...
... tumor antigens, alloantigens, and self-antigens in inflamed tissue. Immune recognition of non-self-antigens typically ... CD4+ Foxp3+ Treg cells, as well as CD8+ CD28- regulatory T cells that dampen cytotoxic responses to grafted organs, are thought ... Self-antigens are present due to endogenous expression, importation of antigen from peripheral sites via circulating blood, and ... Upon exposure to a foreign antigen, either the antigen is eliminated by the standard immune response (resistance), or the ...
Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... Lck and/or ZAP-70 can also phosphorylate the tyrosines on many other molecules, not least CD28, LAT and SLP-76, which allows ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help.[57] Antigen ... Antigen discrimination[edit]. A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. ...
Importantly, the B7-CD28 binding additionally instructs the T cell to produce CTLA-4 (the competitor for CD28). Since CTLA-4 ... This is also called "Signal 1" and its main purpose is to guarantee antigen specificity of the T cell activation. However, MHC ... The proteins CD28 and CTLA-4 (CD152) each interact with both B7-1 and B7-2. There are several steps to activation of the immune ... 2) The signal from the T cell to the APC informs the APC to express B7 (which can be either B7.1 or B7.2). It is the B7-CD28 ...
In T cells, the antigen receptor (TCR) and costimulatory receptors (CD28 and ICOS) are thought to be main receptors responsible ... Genetic inactivation of p110δ in mice causes T cells to be less responsive to antigen as determined by their reduced ability to ... In immune cells, antigen receptors, cytokine receptors and costimulatory and accessory receptors stimulate tyrosine kinase ... August 2002). "Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice". Science. 297 (5583): ...
CD28/CD19) play an important role because they can improve the antigen/receptor binding and initiate parallel cascade events, ... These receptors, that recognize the antigen soluble (B cells) or linked to a molecule on Antigen Presenting Cells (T cells), do ... The antigen receptor and signal protein form a stable complex, named BCR or TCR, in B or T cells, respectively. The family Src ... Therefore, the antigenic receptors play a central role in signal transduction in lymphocytes, because when antigens interact ...
... foreign transplants and cancer cell neo-antigens. Rudd also uncovered signaling mechanisms by which co-receptors CD28, CTLA-4 ... 1989) The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc. ... Rudd's work has had important clinical outcomes as it laid the foundation for chimeric antigen receptor (CAR) cancer therapy ... as well as CD28 signaling motifs that were identified by Rudd's lab. Rudd has received awards including the Cancer Research ...
MHC complex on a professional antigen-presenting cell and by the B7:CD28 costimulatory signal. Upon activation, "low-affinity" ...
"Antigen-dependent CD28 Signaling Selectively Enhances Survival and Proliferation in Genetically Modified Activated Human ... Sadelain is a recognized leader in the concept and design of synthetic receptors for antigen, which he named chimeric antigen ... He is best known for his major contributions to T cell engineering and chimeric antigen receptor (CAR) therapy, an ... 10,370,452 covering compositions and uses of effector T cells expressing a chimeric antigen receptor (CAR), where such T cells ...
CD4+ T细胞的激活需要T细胞上的TCR和共受体(CD28或ICOS),抗原呈递细胞上的MHCII和共激活分子两对分子的分别,同时结合。仅其中一对的结合,无法产生有效的T细胞激活。理想的CD8+ T细胞激活则依赖于CD4+ T细胞的信号转导[28]。 ... MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proceedings of the National ... An induced rebinding model of antigen discrimination. Trends
CD28 • CD29 • CD30 • CD31 • CD32 (A, B) • CD33 • CD34 • CD35 • CD36 • CD37 • CD38 • CD39 • CD40 • CD41 • CD42 (a, b, c, d) • ... 2000). "Characterization of a new member of the TNF family expressed on antigen presenting cells.". Biol. Chem. 380 (12): 1443- ... "BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells.". Semin ...
MHC complex on a professional antigen-presenting cell and by the B7:CD28 costimulatory signal. Upon activation, "low-affinity" ...
I. Partial characterization of soluble Ki-1 antigen and detection of the antigen in cell culture supernatants and in serum by ... Josimovic-Alasevic O, Dürkop H, Schwarting R, Backé E, Stein H, Diamantstein T (Jan 1989). "Ki-1 (CD30) antigen is released by ... CD30+Antigens at the US National Library of Medicine Medical Subject Headings (MeSH) ... results from cDNA cloning and sequence comparison of the CD30 antigen from different sources". Molecular Immunology. 31 (17): ...
Macrophage-1 antigen (CD11b+CD18). *VLA-4 (CD49d+CD29). *Glycoprotein IIb/IIIa (ITGA2B+ITGB3) ...
Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors" ... the intracellular region of a costimulatory molecule such as CD28, and the intracellular domain of CD3-zeta containing ITAM ... TdT is a protein expressed early in the development of pre-T and pre-B cells, whereas CALLA is an antigen found in 80% of ALL ... Chimeric antigen receptors (CARs) have been developed as a promising immunotherapy for ALL. This technology uses a single chain ...
Seligman P. A., Butler C. D., Massey E. J., etal. The p97 antigen is mapped to the q24-qter region of chromosome 3; the same ... Le Beau M. M., Diaz M. O., Plowman G. D., etal. Chromosomal sublocalization of the human p97 melanoma antigen. (англ.) // Hum. ... Plowman G. D., Brown J. P., Enns C. A., etal. Assignment of the gene for human melanoma-associated antigen p97 to chromosome 3 ... Rose T. M., Plowman G. D., Teplow D. B., etal. Primary structure of the human melanoma-associated antigen p97 ( ...
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) also known as CD66e (Cluster of Differentiation 66e), is a ... 2001). "Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells". J. Biol. Chem. 276 ( ... CEACAM5, CD66e, CEA, carcinoembryonic antigen related cell adhesion molecule 5. External IDs. HomoloGene: 128801 GeneCards: ... Oikawa S, Nakazato H, Kosaki G (1987). "Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence". ...
The protein also carries the Jr(a) antigen, which defines the Junior blood group system.[9] ...
van Rhenen A., van Dongen G. A., Kelder A., et al. The novel AML stem cell associated antigen CLL-1 aids in discrimination ...
"Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Molecular and ...
Ebert LM, McColl SR (2002). "Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes ... This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may ... dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens". J. Immunol. 167 (11): ...
limfocyty CD8+CD28−[27] - utożsamiane z wcześniejszymi limfocytami Ts, również nie posiadają ekspresji czynnika Foxp3. ... Antigen-specific peripheral shaping of the natural regulatory T cell population. „J Exp Med". 205 (13), s. 3105-3117, grudzień ... Rola CD28 polega na wzmacnianiu sygnału biegnącego od TCR[40][45]. Jest to zbieżne z obserwacjami dotyczącymi wysokiego ... De novo production of antigen-specific suppressor cells in vivo. „Nat Protoc". 1 (2), s. 653-661, 2006. PMID: 17802642. ...
It is also called Lewis x and SSEA-1 (stage-specific embryonic antigen 1) and represents a marker for murine pluripotent stem ... CD15 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) ... CD15 (3-fucosyl-N-acetyl-lactosamine) is a cluster of differentiation antigen - an immunologically significant molecule. CD15 ...
A new ligand for human leukocyte antigen class II antigens". The Journal of Experimental Medicine. 176 (2): 327-37. doi:10.1084 ... A new ligand for human leukocyte antigen class II antigens". The Journal of Experimental Medicine. 176 (2): 327-37. doi:10.1084 ... antigen processing and presentation of exogenous peptide antigen via MHC class II. ... antigen binding. • transmembrane signaling receptor activity. • MHC class II protein binding. Cellular component. • membrane. • ...
CD28 • CD29 • CD30 • CD31 • CD32 (A, B) • CD33 • CD34 • CD35 • CD36 • CD37 • CD38 • CD39 • CD40 • CD41 • CD42 (a, b, c, d) • ... CD97 antigen je protein koji je kod ljudi kodiran CD97 genom.[1][2][3] ... 2001). "Tissue distribution of the human CD97 EGF-TM7 receptor". Tissue Antigens 57 (4): 325-31. PMID 11380941. doi:10.1034/j. ... "Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of ...
"Entrez Gene: ITGB3 integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)".. *^ May, K. E.; Villar, J.; Kirtley, S.; ... CD61+Antigens at the US National Library of Medicine Medical Subject Headings (MeSH) ...
Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... Lck and/or ZAP-70 can also phosphorylate the tyrosines on many other molecules, not least CD28, LAT and SLP-76, which allows ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help.[51] Antigen ... Antigen discriminationEdit. A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. ...
The positive B cell signaling is initiated by binding of foreign antigen to surface immunoglobulin. The same antigen-specific ... the blockade of CD28 cosignaling does not inhibit the development of TFH cells, a key subset for the generation of autoantibody ... IgE antibodies bind to antigens of allergens. These allergen-bound IgE molecules interact with Fcε receptors on the surface of ... When an appropriate allergic antigen or parasite is present, the cross-linking of a least two of IgE molecules and their Fc ...
"Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science. 261 (5120): 466-9. doi:10.1126/ ...
Past this period CD3 blocks the TCR-antigen binding and causes conformational change or the removal of the entire TCR3/CD3 ... Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling". BMC Immunology. 13: 12. doi:10.1186/1471-2172 ... The IL-2a (CD25, T-cell activation antigen, TAC) is expressed only by the already-activated T lymphocytes. Therefore, it is of ... The antilymphocyte (ALG) and antithymocyte antigens (ATG) are being used. They are part of the steroid-resistant acute ...
B cells can present antigens to a specialized group of helper T cells called TFH cells. If an activated TFH cell recognizes the ... Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help". Journal of Immunology. 149 (12): ... It binds to CD40 (protein) on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In ... Grewal, IS; Xu, J; Flavell, RA (7 December 1995). "Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand". ...
antigen processing and presentation of peptide antigen via MHC class I. • antigen processing and presentation of exogenous ... antigen processing and presentation of exogenous peptide antigen via MHC class I. • lipoprotein transport. • negative ... peptide antigen via MHC class I, TAP-dependent. • platelet degranulation. • MyD88-dependent toll-like receptor signaling ...
Primarily, the VCAM-1 protein is an endothelial ligand for VLA-4 (Very Late Antigen-4 or integrin α4β1) of the β1 subfamily of ...
... uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate (англ.) // Blood (англ ...
In addition to aiding with cytotoxic T cell antigen interactions the CD8 co-receptor also plays a role in T cell signaling. The ... the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell antigen interactions. ... This affinity keeps the T cell receptor of the cytotoxic T cell and the target cell bound closely together during antigen- ... Once the T cell receptor binds its specific antigen Lck phosphorylates the cytoplasmic CD3 and ζ-chains of the TCR complex ...
Takeda K, Harada Y, Watanabe R, Inutake Y, Ogawa S, Onuki K, Kagaya S, Tanabe K, Kishimoto H, Abe R (December 2008). "CD28 ... Goodpasture-antigen-binding protein kinase (EC *-. IκB kinase (EC *CHUK ... "Vav synergizes with protein kinase C theta to mediate IL-4 gene expression in response to CD28 costimulation in T cells". J. ...
antigen binding. • virus receptor activity. • protein binding. • transmembrane signaling receptor activity. • identical protein ...
CD28 • CD29 • CD30 • CD31 • CD32 (A, B) • CD33 • CD34 • CD35 • CD36 • CD37 • CD38 • CD39 • CD40 • CD41 • CD42 (a, b, c, d) • ... 1996). "CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and react with a desmosomal antigen in human ...
Antigens, cd28 explanation free. What is Antigens, cd28? Meaning of Antigens, cd28 medical term. What does Antigens, cd28 mean? ... Looking for online definition of Antigens, cd28 in the Medical Dictionary? ... CD28. (redirected from Antigens, cd28) CD28. a type I transmembrane protein present on most CD4 T cells, many CD8 T cells, and ... Antigens, cd28 , definition of Antigens, cd28 by Medical dictionary ...
CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. ... The B7-CD28 superfamily. Nat Rev Immunol. 2002;2(2):116-126.. View this article via: PubMed CrossRef Google Scholar ... One CAR encoded both the costimulatory CD28 and the ζ-endodomains, while the other encoded only the ζ-endodomain. CAR+ T cells ... Sadelain M, Brentjens R, Riviere I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009; ...
CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. ... CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. ... One CAR encoded both the costimulatory CD28 and the ζ-endodomains, while the other encoded only the ζ-endodomain. CAR+ T cells ... Targeted T cell immunotherapies using engineered T lymphocytes expressing tumor-directed chimeric antigen receptors (CARs) are ...
The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression.. J A Gross, T St John and ... The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression. ... The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression. ... The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression. ...
Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation.. P S ... Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. ... Here we show that CD28 is the primary receptor for B7 on activated peripheral blood T cells, that CD28 binds to B7 in the ... To characterize the binding of CD28 to B7, we have produced genetic fusions of the extracellular portions of B7 and CD28, and ...
... anti-CD3/CD28 (1°) followed by anti-CD3/CD28 (2°) (light gray bars), and anti-CD3/CD28/CTLA-4 (1°) followed by anti-CD3/CD28 (2 ... Coreceptors CD28 and cytotoxic T lymphocyte antigen (CTLA)-4 have opposing effects on TcR/CD3 activation of T cells. While CD28 ... and that this antigen receptor-mediated effect is potentiated by anti-CD28 ligation. CD28 therefore does not provide a unique ... and coreceptors CD28, inducible costimulator (ICOS), and cytotoxic T lymphocyte antigen (CTLA)-4 (CD152) (1, 2). CD28 and CTLA- ...
Design and Methods Our artificial antigen-presenting cells were generated with activating (anti-CD3), co-stimulating (anti-CD28 ... The activity of our artificial antigen-presenting cells was compared with that of anti-CD3/-CD28 coated immunomagnetic ... The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the ... The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the ...
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor ... CD28 Antigens. Known as: TP44 Receptor, Antigens, CD28, CD28 (More). Costimulatory T-LYMPHOCYTE receptors that have specificity ... Antigen-specific targeting of CD28-mediated T cell co-stimulation using chimeric single-chain antibody variable fragment-CD28 ... Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell- ...
... we investigated the effect of adding combined CD28 and 4-1BB costimulatory signaling domains to a chimeric antigen receptor ( ... CAR) specific for prostate-specific membrane antigen (PSMA). Having transferred receptors e … ... To enhance the strength of activation afforded by tumor antigen-specific receptors, ... Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell- ...
A counter-receptor for CD28 is the B7 molecule expressed on activated B cells, dendritic cells, and macrophages. B7 also binds ... The CD28 receptor is stimulated during the contact of T cells with antigen-presenting cells. ... to CTLA-4, a receptor that is structurally related to CD28. CTLA-4 is expressed … ... The CD28 receptor is stimulated during the contact of T cells with antigen-presenting cells. A counter-receptor for CD28 is the ...
CD28" by people in this website by year, and whether "Antigens, CD28" was a major or minor topic of these publications. ... "Antigens, CD28" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Below are the most recent publications written about "Antigens, CD28" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Antigens, CD28". ...
CD28 co-stimulation induced Lck signaling is important for survival and antigen-specific functionality of re-directed T cells. ... Gulati, P., Schuberth, P., Renner, C. et al. CD28 co-stimulation induced Lck signaling is important for survival and antigen- ... We deleted the Lck binding moiety in the CD28 domain of our CAR constructs. The effect of Lck deletion on antigen specific ... Thus, we conclude that Lck signaling mediated by CD28 co-stimulation is important to promote the survival by antigen-specific ...
Flow Cytometry Shop CD3/CD28 Mouse anti-Human, FITC, PE, ... CD3/CD28 Antibody FITC, PE conjugate, MA1-12098, from ... T-cell surface antigen T3/Leu-4 epsilon chain, T-cell surface glycoprotein CD3 epsilon chain, MGC138290, Tp44, CD28 antigen, T- ... Human CD28 antigen is a 44 kDa disulfide linked homodimeric T cell specific surface glycoprotein. It is a cell adhesion ... Activation of T cells results in enhanced CD28 expression. T cell activation requires two combined signals provided by antigen ...
The past years have witnessed significant advance in our understanding of critical roles of T cell co-signals in B7-CD28 family ... 0/Antigens, CD; 0/Antigens, CD28; 0/Antigens, CD80; 0/Antigens, CD86; 0/Antigens, Differentiation; 0/Antigens, Differentiation ... Antigens, CD. Antigens, CD28 / immunology*. Antigens, CD80 / immunology*. Antigens, CD86 / immunology*. Antigens, ... Antigens, Differentiation, T-Lymphocyte / immunology. Humans. Lymphocyte Activation. Receptors, Immunologic / immunology. ...
Cd28. CD28 antigen. 1.64. Mt3. metallothionein 3. 1.69. 1 Predicted mRNA targets, which have a context++ score ≤−0.2, were ... Takeda, K.; Harada, Y.; Watanabe, R.; Inutake, Y.; Ogawa, S.; Onuki, K.; Kagaya, S.; Tanabe, K.; Kishimoto, H.; Abe, R. Cd28 ... and Cd28 (fold change = 1.64; p = 0.05). In contrast to the female placentas, the expression of Gja4 in the male placentas of ... and Cd28 [73]). These processes affect placental trophoblast survival and migration, and the remodeling of the maternal ...
... human-CD28 and which activate non-specifically human-T-lymphocytes of several to all sub-groups without occupying an antigen ... human-CD28 and which activate non-specifically human-T-lymphocytes of several to all sub-groups without occupying an antigen ... HUMAN-CD28 SPECIFIC MONOCLONAL ANTIBODIES FOR ANTIGEN NON-SPECIFIC ACTIVATION OF T-LYMPHOCYTES - [origin: DE19722888A1] The ... HUMAN-CD28 SPECIFIC MONOCLONAL ANTIBODIES FOR ANTIGEN NON-SPECIFIC ACTIVATION OF T-LYMPHOCYTES. Title (en). HUMAN-CD28 SPECIFIC ...
Role of CD80 and CD86 interactions with CD28 and CTLA-4. It is known that low levels of costimulatory molecule (CD80 and CD86) ... Selective enhancement of B cell antigen receptor-mediated antigen presentation by treatment with transforming growth factor-β. ... A bone marrow-derived APC in the gut-associated lymphoid tissue captures oral antigens and presents them to both CD4+ and CD8+ ... CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. Eur. J. Immunol. 32:2997. ...
...请您点击此链接查看产品说明书 CD28 AntibodyRabbit PolyclonalCatalog N… ... Cell Adhesion Molecules, CAM Ligands, Cellular Antigens, Immune System, Infectious Diseases, Metabolic Disorders, Signaling ... T-cell-specific surface glycoprotein CD28 (CD28) is involved in T-cell activation, the induction of cell proliferation, and ... CD28 is expressed in T-cells and plasma cells, but not in less mature B-cells
CD28 : CD80 interactions mediate antigen independent T cell adhesion and ring junction formation ... CD28 : CD80 interactions mediate antigen independent T cell adhesion and ring junction formation ...
Nef Increases Activation by T Cell Antigen Receptor and CD28 Costimulation But Not by Chemical Mitogenic Stimulation.. Because ... Two hundred thousand rested cells and 6 × 105 beads-precoated with anti-CD3 and anti-CD28 mAbs-were added to each well of a U- ... The next day, 2 × 105 cells negative for trypan blue and 6 × 105 beads-precoated with anti-CD3 and anti-CD28-were added to each ... 2 A and B). However, when stimulated with anti-CD3 and anti-CD28, cells expressing Nef showed a marked enhancement of IL-2 ...
... γδT cells or αβT cells from the same donors stimulated with weekly CD3/CD28 beads at the same time points. CD3/CD28 beads were ... Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules. Mol Ther 2007;15:981-8. ... Combined with the antigen-presenting function of γδT cells, this may prove to be an optimal adoptive cell therapy approach for ... Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma. Cancer Immunol Immunother 2005;54:400-6 ...
Antigen Expression CD11a +; CD19 +; CD20 +; CD28 +; CD38 -; CD49e +. Comments The cells are positive for Epstein-Barr nuclear ... Generation of human monoclonal antibodies reactive with cellular antigens. Proc. Natl. Acad. Sci. USA 80: 2026-2030, 1983. ... Generation of human monoclonal antibodies reactive with cellular antigens. Proc. Natl. Acad. Sci. USA 80: 2026-2030, 1983. ...
Mouse monoclonal CD28 antibody [CB28] - BSA and Azide free. Validated in Flow Cyt, ICC/IF and tested in Human. Immunogen ... T cell antigen CD28 antibody. *T cell specific surface glycoprotein antibody. *T cell specific surface glycoprotein CD28 ... Anti-CD28 antibody [CB28] - BSA and Azide free. See all CD28 primary antibodies. ...
Mouse monoclonal CD28 antibody [CD28.2] conjugated to PE/Cy7®. Validated in Flow Cyt and tested in Human. Immunogen ... T cell antigen CD28 antibody. *T cell specific surface glycoprotein antibody. *T cell specific surface glycoprotein CD28 ... Primary - Mouse Anti-CD28 antibody [CD28.2] (PE/Cy7®) (ab234276) Flow Cyt Protein - Recombinant Human CD28 protein (His tag) ( ... Anti-CD28 antibody [CD28.2], prediluted (PE/Cy7®) (ab155387) *Anti-CD28 antibody [CD28.2], prediluted (PerCP/Cy5.5®) (ab157318 ...
... and anti-CD28 (16-0289; eBioscience) for 10 min at 37 °C. Antibodies were adsorbed onto surfaces by incubation of clean glass ... S2C, S4C, S5 A and B, S7A, and S11B). For antigen-stimulated Jurkat-ILA1 cells, nontriggered clusters had an average of 3 CD3ζ ... Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide ... 1989) Role of the zeta chain in the expression of the T cell antigen receptor: Genetic reconstitution studies. EMBO J 8(12): ...
Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell ... demonstrated that CD28-CART cells were superior to CD28-OX40-CART cells because the CD28-OX40 super-costimulation increased ... antigens such as tissue/lineage antigens, developmental antigens, and overexpressed antigens [23]. Most of the recent studies ... C. M. Kowolik, M. S. Topp, S. Gonzalez et al., "CD28 costimulation provided through a CD19-specific chimeric antigen receptor ...
... lymphocyte antigen receptor; cd28 antigen; antigens, cd28; glutamate carboxypeptidase ii; antigens, surface; cd137 antigen; ... Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI 3 kinase/AKT/Bcl-X L activation and CD8 T cell ... Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI 3 kinase/AKT/Bcl-X L activation and CD8 T cell ... Combined Cd28 And 4 1 Bb Costimulation Potentiates Affinity Tuned Chimeric Antigen Receptor Engineered T Cells ...
CD28 : CD80 interactions mediate antigen independent T cell adhesion and ring junction formation ... CD28 : CD80 interactions mediate antigen independent T cell adhesion and ring junction formation ... CD28 : CD80 interactions mediate antigen independent T cell adhesion and ring junction formation ...
Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T ... Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T ... T1 - Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) ... Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T ...
Antigen Expression HLA A1, A33/31, B7, B18, DRw1, DRw2; CD11a +; CD19 +; CD20 + CD28 -; CD38 + ...
  • Here we show that CD28 is the primary receptor for B7 on activated peripheral blood T cells, that CD28 binds to B7 in the absence of other accessory molecules, and that interaction between CD28 and B7 is costimulatory for T cell activation. (
  • T cell activation is mediated by the antigen-receptor complex (TcRζ/CD3) and coreceptors CD28, inducible costimulator (ICOS), and cytotoxic T lymphocyte antigen (CTLA)-4 (CD152) ( 1 , 2 ). (
  • To enhance the strength of activation afforded by tumor antigen-specific receptors, we investigated the effect of adding combined CD28 and 4-1BB costimulatory signaling domains to a chimeric antigen receptor (CAR) specific for prostate-specific membrane antigen (PSMA). (
  • Having transferred receptors encompassing the CD28, 4-1BB, and/or CD3zeta cytoplasmic domains in primary human CD8(+) T cells, we find that the P28BBz receptor, which includes all three signaling domains, is superior to receptors that only include one or two of these domains in promoting cytokine release, in vivo T-cell survival and tumor elimination following intravenous T-cell administration to tumor-bearing severe combined immunodeficient (SCID)/beige mice. (
  • The CD28 receptor is stimulated during the contact of T cells with antigen-presenting cells. (
  • A counter-receptor for CD28 is the B7 molecule expressed on activated B cells, dendritic cells, and macrophages. (
  • B7 also binds to CTLA-4, a receptor that is structurally related to CD28. (
  • Therefore, CD28 receptor stimulation is required for T cell responses to antigens and for B cell responses to T-dependent antigens. (
  • During T cell responses to antigens, CD28 receptor stimulation may be required to prevent clonal inactivation or anergy. (
  • CD28 receptor ligation induces tyrosine phosphorylation of specific substrates, including phospholipase C gamma 1, and triggers both calcium-dependent and calcium-independent signals. (
  • The CD28 costimulatory receptor represents a novel target for immunosuppressive drugs. (
  • T cell activation through the antigen receptor (TCR) involves the cytoplasmic tails of the CD3 subunits CD3 gamma, CD3 delta, CD3 epsilon and CD3 zeta. (
  • DE19722888A1 ] The invention relates to human-compatible monoclonal antibodies, which are specific against human-CD28 and which activate non-specifically human-T-lymphocytes of several to all sub-groups without occupying an antigen receptor of said human-T-lymphocytes. (
  • However, Nef increases IL-2 secretion when cells are stimulated through the T cell receptor and the costimulus receptor (CD28). (
  • Furthermore, HIV infection of the human T cell line Jurkat, as well as primary human T cell cultures, has been shown to enhance T cell activation as mediated by antibody engagement of the T cell receptor and the CD28 coreceptor ( 9 ). (
  • Consistent with in vivo effects, we find that Nef can enhance human T cell activation, but only when cells are stimulated by engaging the T cell receptor and the CD28 coreceptor. (
  • Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. (
  • Recently, chimeric antigen receptor-modified T- (CART-) cell-based therapy, an innovative approach to tumor treatment, was demonstrated to potentially exhibit MHC-independent antitumor effects. (
  • These cells could directly recognize tumor cells by genetic modification to express a chimeric antigen receptor (CAR), and they were activated to exhibit a durable persistence in vivo through the T-cell activation endodomain with costimulatory signaling molecules [ 1 , 2 ]. (
  • Current status of clinical trials of chimeric antigen receptor-modified T (CART) cells in malignancies. (
  • It is the critical T-cell co-stimulatory receptor which provides to the cell the important second activation signal by binding CD80 and CD86 that are expressed by antigen presenting cells. (
  • Antigen-specific T cell activation depends on T cell receptor (TCR) interaction with peptide/major histocompatibility complex (MHC) in conjunction with co-stimulatory signals mediated by accessory molecules. (
  • Several investigators have suggested that the interaction of the CD28 molecule on the T cell with a ligand, B7, on the antigen-presenting cell (APC) is best characterized among the many cell surface receptor/ligand pairs in delivering this costimulatory activity. (
  • This protein receptor on the T cells has the capacity to specifically recognize and bind to a protein on the leukemia or myeloma cells called the 'Lewis Y' antigen. (
  • In addition to signaling by the T cell receptor (TCR), signaling by the costimulatory receptor CD28 is required for full activation of naïve T cells and the generation of regulatory T (T reg ) cells. (
  • The T cell costimulatory receptor CD28 is required for the full activation of naïve T cells and for the development and maintenance of Foxp3 + regulatory T (T reg ) cells. (
  • Signaling through the T cell costimulatory receptor CD28 is essential for the full activation of naïve T cells and their differentiation into effector cells. (
  • CD28 is a cell-adhesion molecule (CAM) that functions as a receptor for CD80 (B7-1) and CD86 (B7-2) antigens, which are present on activated B lymphocytes, monocytes, and dendritic cells. (
  • Interaction of the CD28 antigen with CD80 or CD86 antigens, or both, co-stimulates CD2 and CD3 antigen/T-cell antigen receptor (TCR)-dependent T-cell-mediated proliferation and cytotoxicity. (
  • Moreover, CD28 is the critical T cell costimulatory receptor that provides the cell the important second activation signal by binding CD80 and CD86 which are expressed by antigen presenting cells. (
  • These antigens include CD69, IL-2 receptor (CD25), transferring receptors (CD71), and major histocompatibility complex class II molecules (human leukocyte antigen DR). (
  • The vector of anti-CD23 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human CD23. (
  • CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells (APC). (
  • And CD28 results in a brightly expressed, stable receptor as the transmembrane domain. (
  • On the basis of preclinical observation, this molecule can promote the persistence of antigen-specific and antigen-nonspecific chimeric antigen receptor T-cells to significantly increases antitumor activity. (
  • We find that B lymphocytes rapidly increase glucose uptake and glycolysis following B-cell antigen receptor (BCR) crosslinking. (
  • Most investigations in B cells have focused on the role of genes whose function are important for B-cell antigen receptor (BCR)-induced protein synthesis and increased cell size. (
  • 4 , 5 It is recognized, however, that antigen receptor-triggered macromolecular synthesis and gene expression places enormous bioenergetic demands on lymphocytes. (
  • CD28 is a homodimeric type I transmembrane protein of the Ig receptor superfamily, composed of disulfide-linked 45 kDa subunits. (
  • 1992) Identification and distribution of the costimulatory receptor CD28 in the mouse. (
  • In this report, we further examined the relationship of each immunosenescence marker (age, T cell receptor excision circle frequency, telomerase expression, percentage of CD28 − CD4 + T cells, percentage of CD28 − CD8 + T cells, and the CD4/CD8 T cell ratio) with additional markers of immune response (serum cytokine and chemokine expression) and measures of gene expression and/or regulation. (
  • The chimeric antigen receptor will also contain a gene segment to make the NKT cells last longer. (
  • The T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the α and β chains, and a signaling subunit, namely the CD3ε, γ and δ chains and the TCRζ chain. (
  • Present cellular therapies include chimeric antigen receptor T cells - genetically modified to attack a specific target and used to treat B cell blood cancers - and tumor-infiltrating leukocytes harvested from tumors used to treat melanoma. (
  • 2 The triggers of activation and expansion of CD4 + CD28 null cells to date remain unclear, although restricted T-cell receptor-β usage points to stimulation by a specific antigen. (
  • In the periphery, one important level of regulation is the action of costimulatory signals in concert with TCR (T-Cell antigen Receptor) signals to promote full T-cell activation (Ref. 1). (
  • Binding of CTLA4 to PI3K indicates that the co-receptor can generate positive signals in common with CD28. (
  • T cell stimulation through CD28 in addition to the T-cell receptor (TCR) can provide a potent signal for the production of various interleukins (IL-6 in particular). (
  • CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins. (
  • When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen-presenting cells (APCs). (
  • CD28 is the only B7 receptor constitutively expressed on naive T cells. (
  • Recently, chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematological tumors and current research is going on in various solid tumors like ovarian cancer. (
  • Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. (
  • Chmielewski M, Hombach AA, Abken H. Antigen-specific T-cell activation independently of the MHC: chimeric antigen receptor-redirected T cells. (
  • Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition. (
  • The authors describe the first human application of autologous chimeric antigen receptor gene-modified T cells targeting TAG-72 in the treatment of metastatic colorectal cancer in two clinical trials. (
  • Although naturally occurring CD4 + CD25 + Tr cells are part of the normal T-cell repertoire, Tr1 cells are induced regulatory cells that can be generated from the peripheral naïve T-cell repertoire after activation via the T-cell receptor (TCR) and chronic exposure to antigen in the presence of exogenous IL-10 ( 5 ). (
  • In addition to CD80 (B7-1), CD86 is a counter-receptor for the T cell surface molecules CD28 and CD152 (CTLA-4). (
  • The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. (
  • For example, disclosed herein are genetically-modified cells comprising a chimeric antigen receptor or an inducible regulatory construct incorporating the co-stimulatory domains disclosed herein. (
  • 15. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein said CAR comprises at least one of said co-stimulatory domains. (
  • This is achieved by interacting with a professional APC which presents an antigen recognized by their T cell receptor. (
  • They are very efficient at internalizing antigens, either by phagocytosis (e.g. macrophages), or by receptor-mediated endocytosis (B cells), processing the antigen into peptide fragments and then displaying those peptides (bound to a class II MHC molecule) on their membrane. (
  • The protumorigenic function of CTLA4 is believed to be limited to T-cell inhibition by countering the activity of the T-cell costimulating receptor CD28. (
  • The glycoprotein CD28 is the receptor of costimulatory signals delivered by antigen-presenting cells through the CD80/CD86 family during T cell activation, and thereby delivers the strongest known "second signal" in the activation and survival of T cells by T cell receptor/CD3 1 . (
  • Targeted T cell immunotherapies using engineered T lymphocytes expressing tumor-directed chimeric antigen receptors (CARs) are designed to benefit patients with cancer. (
  • Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. (
  • Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication. (
  • Antigen-specific targeting of CD28-mediated T cell co-stimulation using chimeric single-chain antibody variable fragment-CD28 receptors. (
  • These findings further support the concept of integrating optimized costimulatory properties into recombinant antigen receptors to augment the survival and function of genetically targeted T cells within the tumor microenvironment. (
  • Chimeric antigen receptors (CARs) are recombinant receptors consisting of an antibody derived antigen binding domain coupled to intracellular T cell signaling domains. (
  • T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies. (
  • In recent years, immunotherapeutic approaches have shown promise in the treatment of CD19 + hematologic malignancies, including the adoptive transfer of T cells expressing CD19-specific chimeric antigen receptors (CAR) or the infusion of bispecific antibodies (BiTE) to redirect T cells to CD19 + tumor cells ( 5-16 ). (
  • In a previous clinical trial, investigators made artificial genes called a chimeric antigen receptors (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). (
  • We will expand NKT cells and add GD2-specific chimeric antigen receptors to the cells. (
  • Besides CD28, many other transmembrane receptors also modulate specific elements of TCR signaling. (
  • 1 These CD4 + CD28 null cells, which in UA may constitute up to 50% of the total CD4 + compartment, express killer immunoglobulin-like receptors, a characteristic of natural killer cells, and have cytolytic function releasing perforin on activation. (
  • A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer. (
  • T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. (
  • Those that express MHC class II molecules along with co-stimulatory molecules and pattern recognition receptors are often called professional antigen-presenting cells. (
  • Once a dendritic cell's pattern-recognition receptors recognize a pathogen-associated molecular pattern, antigen is phagocytosed and the dendritic cell becomes activated, upregulating the expression of MHC class II molecules. (
  • The activity of our artificial antigen-presenting cells was compared with that of anti-CD3/-CD28 coated immunomagnetic microbeads and immobilized anti-CD3 monoclonal antibody (OKT3 clone), the only two commercially available artificial systems. (
  • This antibody is a monoclonal mixture of FITC-conjugated CD3 (clone M2AB, isotype IgG1) and PE-conjugated CD28 (clone B-23, isotype IgG1). (
  • To expand the full repertoire of γδT without bias toward specific TCRs, we made use of artificial antigen-presenting cells loaded with an anti γδTCR antibody that promoted unbiased expansion of the γδT repertoire. (
  • Gamma delta T (γδT) lymphocytes have both cytotoxic and professional antigen-presenting capacity ( 1-4 ), but have been relatively overlooked in terms of their potential role as mediators of antibody-dependent cell-mediated cytotoxicity (ADCC), particularly in the context of mAb treatments of cancer. (
  • There are currently no images for CD28 Antibody (NBP2-34576UV). (
  • There are no publications for CD28 Antibody (NB100-65334PE). (
  • ImmunoCult™ Human CD3/CD28 T Cell Activator consists of soluble tetrameric antibody complexes that bind CD3 and CD28 cell surface ligands. (
  • Binding of the tetrameric antibody complexes results in the cross-linking of CD3 and CD28 cell surface ligands, thereby providing the required primary and co-stimulatory signals for T cell activation. (
  • The L293 monoclonal antibody specifically binds to CD28 which is also known as Tp44 or T44. (
  • The 37.51 antibody reacts with CD28, which is expressed on most thymocytes, at low density on nearly all CD4+ and CD8+ peripheral T cells, and at even lower density on NK cells. (
  • The following antibody was used in this experiment: CD28 Monoclonal Antibody (CD28.2), PerCP from Thermo Fisher Scientific, catalog # MA1-10171, RRID AB_11154515. (
  • An assessment of functional antibody production in response to natural antigens or antigens to which the population is commonly exposed may be helpful. (
  • Similarly, an evaluation of the antibody response after active immunization with polysaccharide or protein antigens is possible. (
  • The T cells are genetically modified through transduction with a retroviral vector expressing scFv of anti-CD23 antibody linked to CD28 and 41BB and CD3ζ signaling domains. (
  • Description: A polyclonal antibody for detection of CD28 phospho Tyr218) from Human, Mouse. (
  • This CD28 phospho Tyr218) antibody is for WB, ELISA. (
  • Description: Phospho-CD28 (Tyr218) Antibody detects endogenous levels of CD28 only when phosphorylated at Tyr218. (
  • Description: A polyclonal antibody against Phospho-CD28 (Y218). (
  • Description: A Rabbit Polyclonal antibody against CD28 from Human. (
  • Description: A polyclonal antibody raised in Goat that recognizes and binds to Human CD28 (internal region). (
  • Purified CD4 + lymphocytes obtained from uninfected donors were cultured either with PHA and IL-2 or with beads coated with the CD3 monoclonal antibody OKT3 and the CD28 monoclonal antibody 9.3. (
  • Many characteristics of the human CD28 molecule are conserved within the putative murine CD28 polypeptide. (
  • CD28 is a cell adhesion molecule of the immunoglobulin superfamily which is constitutively expressed on most peripheral blood T lymphocytes. (
  • CD19-ENG.41BBL/CD80 T cells retained their antigen specificity and had superior effector function compared with both unmodified T cells and CD19-ENG T cells expressing either CD80, 41BBL, or no costimulatory molecule, as judged by cytokine (IFNγ and IL2) production, T-cell proliferation, and their ability to sequentially kill target cells. (
  • CD28 is considered a major co-stimulatory molecule, inducing T lymphocyte activation and IL-2 synthesis, and preventing cell death. (
  • CD86 acts as costimulatory molecule in eliciting T-cell help during antigen presentation. (
  • The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. (
  • Interaction of the costimulatory molecule CD28 with its ligands CD80 or CD86 provides a necessary costimulus to induce an immune response ( 3 ). (
  • T cell activation requires two combined signals provided by antigen presenting cells. (
  • Ligation of CD28 with CD80 (B7-1) and CD86 (B7-2) provides a costimulatory signal for T cell activation. (
  • The CD86 expression on antigen-presenting cells is constitutive (expression is independent of environmental factors). (
  • CD28 binds both CD80 and CD86 using a highly conserved motif MYPPY in the CDR3-like loop. (
  • In vitro studies indicate that ligation of CD28 on T cells by CD80 and CD86 on antigen presenting cells provides a costimulatory signal required for T cell activation and proliferation. (
  • CD86 is one of two ligands (the other CD80) for CTLA4 and CD28. (
  • Antigen presentation in the absence of sufficient co-stimulation involving CD86/CD80 can induce tolerance. (
  • The CD86 protein is expressed by antigen-presenting cells, and it is the ligand for two proteins at the cell surface of T cells, CD28 antigen and cytotoxic T-lymphocyte-associated protein 4. (
  • Binding of CD86 with CD28 antigen is a costimulatory signal for activation of the T-cell. (
  • Abatacept is a fusion protein (CTLA4-Ig) that can act as a costimulation blocker binding to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T cell activation, and it has proven useful in the treatment of patients with RA, including those refractory to tumor necrosis factor-α (TNF-α) blocking agents 24 , 25 . (
  • In order to identify a reliable method for producing adequate amounts of functional antitumor cytotoxic T lymphocytes with a potentially long in vivo lifespan, we tested the T-cell expansion efficiency of a new artificial antigen-presenting cell-based system. (
  • One of its responses to a foreign antigen is the proliferation of a class of lymphocytes which specifically recognizes the antigen. (
  • It has been reported that CD28 is not expressed on some populations of intraepithelial T lymphocytes. (
  • PPD, streptokinase, Candida antigen, and tetanus toxoid all activate lymphocytes, if the patient has had a prior exposure to the antigen or superantigen. (
  • T lymphocytes express certain antigens after activation. (
  • The bioenergetic response of B lymphocytes is subject to rapid changes following antigen encounter in order to provide ATP and anabolic precursors necessary to support growth. (
  • In response to antigen challenge, resting B lymphocytes exit the G 0 phase of the cell cycle and undergo a period of growth before committing to genome replication. (
  • 3 - 5 That mammalian cell growth may be necessary for genome replication underscores its importance in adaptive immunity in that the clonal expansion of antigen-specific B lymphocytes is a prerequisite for humoral immune responses. (
  • Schwartz, R.H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB 1 in interleukin-2 production and immunotherapy. (
  • Naïve CD4+ cells, lymphocytes which have not yet encountered an antigen, and CD8+ cells also decline. (
  • Activation of CD4 + T lymphocytes from human immunodeficiency virus-type 1 (HIV-1)-infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. (
  • Our observations demonstrate for the first time that CTLA-4 targets the release of rafts to the surface of T cells, and provides a mechanism for the opposing effects of CD28 and CTLA-4 on costimulation. (
  • Although CD28 promotes raft expression, there has been a lack of evidence on whether alterations in the formation of surface rafts can explain the opposing effects of CD28 and CTLA-4 on the costimulation of T cells. (
  • Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. (
  • CD28 costimulation prevents cell death during primary T cell activation. (
  • As BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells. (
  • Porcine aortic endothelial cells activate human T cells: direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28. (
  • Costimulation involves an integration of activating signals and inhibitory signals from CD28 and CTLA4 (Cytotoxic T-Lymphocyte Antigen-4) molecules, respectively, with TCR signals to determine the outcome of a T-cell's encounter with an antigen (Ref. 2). (
  • Tissue-specific, inducible expression of the IL-2Rα gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Rα gene transcription. (
  • Thus, CD3/CD28 costimulation induces an HIV-1-resistant phenotype similar to that seen in some highly exposed and HIV-uninfected individuals. (
  • However, CD3/CD28-stimulated cells express an additional, cis-acting component of resistance specific to costimulation with immobilized anti-CD28 ( 5 ). (
  • To verify the hypothesis that blockade of CD28 costimulation by treatment with abatacept in patients with rheumatoid arthritis (RA) might induce a reduction in the number of CD28- T cells, as well as other effector T cell populations. (
  • Moreover, costimulation through CD28, stabilizing interleukin 2 (IL-2) gene transcription and translation, is critical for IL-2 production by T cells 2 . (
  • Our aim was to verify that blockade of CD28 costimulation by treatment with abatacept in patients with RA refractory to TNF-α inhibition might induce a reduction in the number of circulating CD28- T cells, as well as of other effector T cell populations, and to evaluate whether these variations are correlated with clinical response. (
  • CAR+ T cells containing the CD28 endodomain showed strikingly enhanced expansion and persistence compared with CAR+ T cells lacking this endodomain. (
  • The human T lymphocyte Ag CD28 (Tp44) is a homodimeric glycoprotein expressed on the surface of a majority of human peripheral T cells and thymocytes. (
  • Although exposure of T cells to anti-CD28 mAb does not activate T cells, stimulation of CD28 can synergize with signals transmitted through the TCR or other stimuli to augment proliferation and lymphokine production. (
  • We recently showed that CD28, a T cell surface protein that regulates an activation pathway, could mediate intercellular adhesion with activated B cells by interaction with the B7 antigen. (
  • 125I-labeled B7 Ig bound to CD28-transfected Chinese hamster ovary (CHO) cells, and to immobilized CD28 Ig with a Kd approximately 200 nM. (
  • The function of CD28-B7 interactions during T cell activation was investigated with soluble fusion proteins and with B7-transfected CHO cells. (
  • Cellular interactions mediated by B7 and CD28 may represent an important component of the functional interactions between T and B lymphoid cells. (
  • Coreceptors CD28 and cytotoxic T lymphocyte antigen (CTLA)-4 have opposing effects on TcR/CD3 activation of T cells. (
  • While CD28 increased expression and the number of peripheral T cells induced to express surface rafts in response to TcR ligation, CTLA-4 potently inhibited both TcR and TcR × CD28 induced raft expression on the surface of T cells. (
  • Consistent with this, CD28 increased the presence of the linker of activated T cells (LAT) in purified membrane rafts, while CTLA-4 coligation effectively blocked this increase. (
  • In this study, we report that while CD28 greatly increased the number of GM1 negative peripheral T cells that become positive as a result of TcR ligation, CTLA-4 profoundly inhibited the expression of surface rafts. (
  • This was confirmed biochemically where CD28 augmented the detection of the adaptor LAT in purified rafts, while CTLA-4 coligation blocked this increase at the level of resting T cells. (
  • Design and Methods Our artificial antigen-presenting cells were generated with activating (anti-CD3), co-stimulating (anti-CD28) and adhesion (anti-LFA-1) biotinylated monoclonal antibodies preclusterted in microdomains held on a liposome scaffold by neutravidin rafts. (
  • Results Our artificial antigen-presenting cells expanded both polyclonal T cells and MART-1-specific CD8 + T cells in a more efficient manner than the other systems. (
  • Stimulation with artificial antigen-presenting cells allows for the generation of viable T cells displaying an immunophenotype consistent with in vivo potential for persistence, without increasing the frequency of regulatory T cells. (
  • The starting specificity of anti MART-1 CD8 + T cells was preserved after stimulation with artificial antigen-presenting cells and it was statistically greater when compared to the activity of the same cells expanded with the other systems. (
  • Finally, our artificial antigen-presenting cells proved to be suitable for large-scale application, minimizing the volume and the costs of T-cell expansion. (
  • Conclusions Our artificial antigen-presenting cells might represent an efficient tool to rapidly obtain a sufficient number of functional T cells for adoptive immunotherapy in patients with cancer. (
  • Expansion of cytotoxic CD8+ CD28- T cells in healthy ageing people, including centenarians. (
  • B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. (
  • CTLA-4 is expressed in low copy number by T cells only after activation, but it binds B7 with approximately 20-fold higher affinity than CD28. (
  • T cells were genetically engineered with CARs with pre-defined binding and CD28-CD3ζ signaling to initiate T cell activation. (
  • In future, the efficacy and survival of re-directed T cells with CD28 modification will be studied in a humanized mouse model. (
  • Mature thymocytes exhibit higher levels of CD28 than the immature cells. (
  • Activation of T cells results in enhanced CD28 expression. (
  • CD28 is expressed in T-cells and plasma cells, but not in less mature B-cells. (
  • Here, we show that artificial antigen-presenting cells that can be used within good manufacturing practice (GMP) protocols can result in the unbiased expansion of a wide range of repertoires. (
  • Tissue, cells or virus corresponding to CD28. (
  • Recent published clinical studies on CART cells specific for solid tumor antigens. (
  • Besides its co-stimulation role, CD28 functions in preventing T-cells from anergic hyporesponsive state or from undergoing premature apoptotic cell death. (
  • CD28 is also expressed on human fetal NK cells and some NK cell lines, whereas on murine NK cells the CD28 expression is much broader. (
  • In chickens CD28 is expressed by all T cells excluding T cells that are gamma/delta positive. (
  • Human γ δ T cells display the principal characteristics of professional antigen-presenting cells (APCs), in addition to playing a vital role in immunity through cytokine secretion and their cytotoxic activity. (
  • F1-ATPase) in a manner somewhat analogous to MHC-mediated antigen presentation [ 10 ], suggesting that V γ 9V δ 2 cells can function as professional antigen-presenting cells (APCs) [ 11 - 13 ]. (
  • CD28 is a cell surface glycoprotein constitutively expressed on most T cells, which has been recently shown to interact with B7, which is expressed on dendritic cells, macrophages, and activated B and T cells. (
  • Blocking the binding of CD28 on T cells to its ligand, B7/BB-1, during TCR engagement, results in T cell anergy. (
  • ImmunoCult™ Human CD3/CD28 T Cell Activator is designed to activate and expand human T cells in the absence of magnetic beads, feeder cells, or antigen. (
  • Image of human T cells isolated using the EasySep™ Human T Cell Isolation Kit (Catalog #17951), stimulated with ImmunoCult™ Human CD3/CD28 T Cell Activator, and cultured in ImmunoCult™-XF T Cell Expansion Medium (Catalog # 10981). (
  • Mice with T cells expressing a mutant CD28 devoid of its C-terminal basic amino acids were defective in T reg cell generation. (
  • We showed that the cytoplasmic domain of CD28 was bound to the plasma membrane in resting cells and that ligand binding to CD28 resulted in its release. (
  • Consequently, mutation of either a basic cluster or Tyr 207 impaired CD28 function in mice as shown by the reduced thymic differentiation of FoxP3 + T reg cells. (
  • CD4+CD28null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon-gamma and perforin mRNA transcription as criteria for activation. (
  • Incubation of the cells with anti-MHC class II and anti-CD4 antibodies but not anti-class I antibodies blocked antigen presentation, confirming recognition of the hHSP60 to be via the MHC class II pathway. (
  • These cells were nonreactive to any of the antigens used. (
  • CONCLUSIONS: We have shown that hHSP60 is an antigen recognized by CD4+CD28null T cells of ACS patients. (
  • The CD28 antigen is a 44 kDa homodimeric type I transmembrane glycoprotein which is present on most mature T cells, thymocytes, and plasma cells. (
  • CD28 transcripts are found in mast cells, and cell-surface expression of CD28 is induced upon maturation or activation of mast cells. (
  • In addition to its co-stimulation role, CD28 functions by preventing T cells from entering an anergic-hyporesponsive state or from undergoing premature apoptotic cell death. (
  • In murine peripheral lymphoid organs and in the blood, all CD4+ and CD8+ T cells express CD28. (
  • In the thymus, CD28 expression is highest on immature CD3-, CD8+ and CD4+8+ cells, and on CD4-8- cells that express alpha/beta and gamma/delta TCR. (
  • The level of CD28 on mature CD4+ and CD8+ alpha/beta TCR+ thymocytes is two- to fourfold lower than on the immature cells. (
  • Species-specific monoclonal antibodies suggest that PAECs directly present swine MHC antigens to human T cells and that human CD4 and CD8 molecules participate in this interaction. (
  • Furthermore, PAECs bind CTLA-4-Ig and costimulate human T cells by both the CD2 and CD28 pathways. (
  • CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. (
  • CAR+ T cells containing the CD28 endodomain showed strikingly enhanced sustained T cell activation, growth, survival. (
  • It is expressed mainly on activated CD4+ and CD8+ T cells, and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. (
  • Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules. (
  • To facilitate the therapeutic application of antigen-presenting cells (APCs), we have developed a cell-based artificial APC (aAPC) system by engineering K562 cells with lentiviruses to direct the stable expression and secretion of a variety of co-stimulatory molecules and cytokines. (
  • Finally, the aAPCs provide an efficient platform to expand genetically modified T cells and to maintain CD28 expression on CD8 T cells. (
  • Through the combined effects of positive and negative selection, T cell differentiation in the thymus generates a repertoire of mature T cells that is tailored to tolerate self antigens but mount strong responses to foreign antigens 1,2 . (
  • Furthermore, the percent of CD4 + and/or CD8 + T cells lacking CD28 expression also correlated with miRNAs regulating clusters of genes known to be involved in viral infection. (
  • This complex participates in T-cell activation upon the presentation of the antigen peptide (derived from the foreign antigen) bound to the MHC (Class I and Class II) residing on antigen-presenting cells (APCs), including dendritic cells, macrophages and B cells. (
  • We present here a method to develop functional antigen (Ag)-specific regulatory T cells (Tregs) from induced pluripotent stem cells (iPSCs) for immunotherapy of autoimmune arthritis in a murine model. (
  • Cellular therapies produce mainly effector CD8-positive T cells that are fully differentiated to attack cells bearing specific antigens. (
  • Surprisingly, B. abortus induced down-regulation of CD28 and up-regulation of B7.2 on murine CD4 + and CD8 + T cells. (
  • These effects on T cells were maximal for CD28 and B7.2 at 40 to 48 h and were not dependent on interleukin-12 (IL-12) or IFN-γ. (
  • We suggest that down-regulation of CD28 following activation inhibits subsequent differentiation of Th0 into Th2 cells. (
  • In addition, decreased expression of CD28 and increased expression of B7.2 on T cells would favor B7.2 interaction with CTLA-4 on T cells, and this could provide a negative signal to developing Th2 cells. (
  • For example, when an antigen-presenting cell expresses an antigen on MHC class II , a CD4 + cell will aid those cells through a combination of cell to cell interactions (e.g. (
  • It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. (
  • Class II MHC proteins are generally only found on the surface of specialised antigen-presenting cells (APCs). (
  • Specialised antigen presenting cells are primarily dendritic cells , macrophages and B cells , although dendritic cells are the only cell group that expresses MHC Class II constitutively (at all times). (
  • Some APCs also bind native (or unprocessed) antigens to their surface, such as follicular dendritic cells , but unprocessed antigens do not interact with T cells and are not involved in their activation. (
  • Antigen presentation stimulates naïve CD8+ and CD4+ T cells to respectively become mature "cytotoxic" CD8+ cells and "helper" CD4+ cells. (
  • During an immune response, professional antigen-presenting cells (APCs) endocytose foreign material (typically bacteria or viruses ), which undergoes processing , then travel from the infection site to the lymph nodes . (
  • Once at the lymph nodes, the APCs begin to present antigen peptides that are bound to Class II MHC, allowing CD4 + T cells that express the specific TCRs against the peptide/MHC complex to activate. (
  • Background- CD4 + CD28 null T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome (ACS) compared with patients with chronic stable angina (CSA). (
  • CD4 + CD28 null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon-γ and perforin mRNA transcription as criteria for activation. (
  • CD4 + CD28 null cells from 12 of 21 patients with ACS reacted with hHSP60. (
  • Patients with CSA had low numbers of CD4 + CD28 null cells. (
  • Circulating CD4 + CD28 null cells were present in 5 of the 9 healthy controls. (
  • Circulating hHSP60-specific CD4 + CD28 null cells may, along other inflammatory mechanisms, contribute to vascular damage in these patients. (
  • Patients with unstable angina (UA) but not chronic stable angina (CSA) experience expansion of a subset of CD4 + T cells that lack the CD28 marker. (
  • 2 Their ability to produce high levels of interferon (IFN)-γ, together with the finding that CD4 + CD28 null cells can be isolated from ruptured unstable atherosclerotic plaques, supports the notion that alongside other proinflammatory mechanisms, they may have a role in the events leading to plaque destabilization and acute coronary syndromes (ACS). (
  • 6-9 The objective of the present study was to investigate whether any of these antigens act as targets for the CD4 + CD28 null cells. (
  • An understanding of antigen-mediated emergence and expansion of these cells may provide an invaluable insight into a possible contributory pathway of plaque destabilization. (
  • Stimulation of TCR is triggered by MHC (Major Histocompatibility Complex) molecules on antigen presenting cells that present antigen peptides to TCR complexes and induce a series of intracellular signaling cascades that regulate T-cell development, homeostasis, activation, acquisition of effector's functions and apoptosis. (
  • The activation of T-cells by Antigen-MHC-II complex carried on antigen presenting cells is a complex process involving a cascade of events, the first of which is phosphorylation of the PTKs (Protein Tyrosine Kinases) belonging to the Src and SYK ZAP70 (Zeta-Chain-Associated Protein Kinase) families. (
  • As microbicidal activity of macrophages depends on their activation by antigen-specific T-cells, the occurrence of infection could be secondary to interference in the activation process by mycobacteria. (
  • Previously, we have demonstrated the response of crude M. leprae antigens on the signalling mechanism of T-cells[ 16 ] therefore, current study was done to decipher the mechanism of Man-LAM and PGL-1, the lipid components, on signalling events leading to T-cell activation, which still needs documentation. (
  • The concentration of antigens corresponding to log phase of T-cell proliferation, by lymphocyte transformation assay in PBL and Jurkat T cells (data not shown), was considered as optimal for further signalling experiments. (
  • Human CD28 derived in Human Cells. (
  • Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. (
  • Chang CC, Campoli M, Ferrone S. Classical and nonclassical HLA class I antigen and NK Cell-activating ligand changes in malignant cells: current challenges and future directions. (
  • CD28 is expressed on most T lineage cells, NK cell subsets, and plasma cells. (
  • CD4 + T-cells from rapamycin plus IL-10-treated mice transferred antigen-specific tolerance in mice that received new transplants. (
  • Thus rapamycin plus IL-10 not only prevented allograft rejection but also induced Tr1 cells that mediated stable antigen-specific, long-term tolerance in vivo. (
  • After being activated with their specific antigen, Tr1 cells regulate the responses of naïve and memory T-cells in vitro and in vivo and can suppress Th1 cell-and Th2 cell-mediated pathologies ( 4 ). (
  • Although Tr1 cells must encounter their antigen to exert these effects, once the Tr1 cells are activated, they suppress in a non-antigen-specific manner. (
  • These consist of naturally occurring CD25+ Treg cells and adaptive Treg cells that are postulated to prevent immune responses against self-antigens and adaptive immune responses, respectively. (
  • Foreign antigens, including allergens or pathogens, that enter the body are taken up by so-called antigen-presenting cells (APC), which process the antigens and present peptides, thereof, in the context of major histocompatibility complex class (MHC) II molecules on their cell surface. (
  • Once activated, the Th-cells orchestrate adaptive antigen-specific cell-mediated and humoral immune responses. (
  • The use of dendritic cells as host cells enables effective presentation of RNA-encoded antigens in the presence of key factors for induction of potent immune responses. (
  • An alternative strategy pursues direct in vivo administration of antigen-encoding RNA, under the assumption that the cells at the administration site internalize, translate, and present the antigen. (
  • However, induction of antigen-specific CD8 + T cells in patients was moderate ( 8 ), and CD4 + T-cell activity has not been reported. (
  • Moreover, we achieved significant leverage of MHC class I and, importantly, class II presentation of the encoded antigen in dendritic cells by flanking it with a secretion signal (sec) and the transmembrane and cytosolic domains of MHC class I (MITD) molecules ( 10 ). (
  • CD80 dimers on the antigen presenting cells (APCs) bridge CTLA4/CD152 dimers on T-cells in a periodic zipper-like arrangement. (
  • One population of naturally-occurring or endogenous T suppressor cells can be identified by co-expression of the CD4 and CD25 antigens. (
  • CD4+ cells decline in number and gradually lose their ability to respond to stimulation by antigens . (
  • This activation is measured by increased expression of CD38 molecules and human leukocyte antigen on the surface of these cells. (
  • An additional measure of progressive immune deterioration is decreased expression of CD28 molecules on CD8+ cells. (
  • The present disclosure provides novel co-stimulatory domains useful in genetically-modified cells to promote cell proliferation and/or promote cytokine secretion after antigen recognition. (
  • APCs process antigens and present them to T-cells. (
  • Professional antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T cells, while virus-infected cells (or cancer cells) can present antigens originating inside the cell to cytotoxic T cells. (
  • In addition to the MHC family of proteins, antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells. (
  • Antigen-presenting cells are vital for effective adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. (
  • Antigen-presenting cells fall into two categories: professional and non-professional. (
  • T cells cannot recognize (and therefore cannot respond to) "free" or soluble antigens. (
  • They can only recognize and respond to antigen that has been processed and presented by cells via carrier molecules like MHC molecules. (
  • Professional APCs specialize in presenting antigens to T cells. (
  • The main types of professional antigen-presenting cells are dendritic cells, macrophages and B cells. (
  • Dendritic cells have the broadest range of antigen presentation and are necessary for activation of naive T cells. (
  • DCs present antigen to both helper and cytotoxic T cells. (
  • They can also perform cross-presentation, a process by which they present exogenous antigen on MHC class I molecules to cytotoxic T cells. (
  • Prior to encountering foreign antigen, dendritic cells express very low levels of MHC class II and co-stimulatory molecules on their cell surface. (
  • These immature dendritic cells are ineffective at presenting antigen to T helper cells. (
  • Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. (
  • In addition to promoting the long-term polyclonal proliferation of CD4 + T cells in the absence of exogenous cytokines or feeder cells, activation with immobilized antibodies to CD3 (anti-CD3) and CD28 (anti-CD28) specifically induces a potent anti-HIV effect ( 4 ). (
  • This intrinsic CD3/CD28-specific antiviral effect was examined by comparing the HIV-1 infection process in cells stimulated with either immobilized anti-CD3 and anti-CD28 or with the mitogenic lectin phytohemagglutinin (PHA) and interleukin-2 (IL-2). (
  • The cells were infected with either the M-tropic isolate HIV US1 or the TCL-tropic isolate HIV NL4-3 ( 7 ) 3 days after stimulation, and the kinetics of virus replication were assessed by measuring p24 Gag antigen production (Fig. 1 ). (
  • When CD3/CD28-activated CD4 + cells were infected with HIV US1 , p24 Gag antigen production was virtually undetectable throughout the experiment, in agreement with our previous observation that CD3/CD28-activated cells are resistant to infection with the M-tropic isolate HIV Ba-L ( 4 ). (
  • However, when CD3/CD28-stimulated cells were infected with the TCL-tropic isolate HIV NL4-3 , a productive infection ensued (Fig.1). (
  • After 48 weeks of treatment, the proportion and the absolute number of circulating CD8+CD28- T cells decreased (p = 0.008, p = 0.055, respectively, compared with baseline), as well as the proportion of the CD8+CD45RA+CCR7- cells, thought to represent terminally differentiated effector T cells (p = 0.03). (
  • After therapy with abatacept, circulating CD28- T cells and other effector populations decrease in patients with RA. (
  • In healthy individuals, CD28 is constitutively expressed by almost all CD4+ and more than 50% of CD8+ T cells. (
  • The number of CD28- T cells is extremely low in normal newborns 3 , and increases gradually with age 4 . (
  • In RA, the expansion of CD28- T cells is associated with aggressive disease, extraarticular manifestations 13 , and preclinical atherosclerotic changes, including arterial endothelial dysfunction, suggesting that they may contribute to early atherosclerotic damage in these patients 14 . (
  • The CD28- T cell population displays some functional properties of differentiated effector cells 18 , 19 . (
  • CD5 specifically interacts with CD72 antigen (CD72), a cell-surface protein exclusively expressed in B cells. (
  • The development of therapies that specifically target autoreactive immune cells for the prevention and treatment of type 1 diabetes (T1D) without inducing generalized immunosuppression that often compromises the host's ability to clear non-self antigen is highly desired. (
  • The putative mechanisms include, but are not limited to, the uptake and processing of antigen-coupled nanoparticles or apoptotic cellular carriers for tolerogenic presentation by host splenic antigen-presenting cells, the induction of regulatory T cells, and the secretion of immune-suppressive cytokines, such as IL-10 and TGF-β. (
  • The invention relates generally to compositions of and methods for obtaining and using a polypeptide, other than B7, that binds to CTLA4, or CD28, or CTLA4Ig, or homologous proteins, and regulates T cell activation. (
  • SIT (SHP2-Interacting Transmembrane Adaptor Protein) and CTLA4 (Cytotoxic T-Lymphocyte Antigen-4) are transmembrane adaptor proteins that interact with the SHP2 (SH2-containing Protein tyrosine Phosphatase-2) and negatively regulate T-cell activation by inhibiting the phosphorylation of Fyn and CD28 respectively. (
  • Expression of CTLA4 is dependent both on TCR stimulation by the antigens and CD28-B7 engagement. (
  • Accumulation of CD28 occurs during T-cell activation and has also been shown to induce expression of CTLA4 and increase stability of CTLA4 mRNA. (
  • One mechanism involves antagonism of B7-CD28-mediated costimulatory signals by CTLA4, which occurs because CTLA4 has a much higher affinity for B7 than does CD28. (
  • CTLA4 binds CD80/86 500 to 2500 times more avidly than CD28 does. (
  • CTL-associated antigen 4 (CTLA4) is a well-established immune checkpoint for antitumor immune responses. (
  • CTL-associated antigen 4 (CTLA4) is well recognized as an immune checkpoint, and has emerged as a prominent target for cancer immunotherapy ( 1, 2 ). (
  • Information concerning the role of ligand interaction with CD28 can be found in PCT Application Number PCT/US89/05304, published as International Publication Number WO90/05541, the disclosure of which is incorporated herein by reference. (
  • Ligand binding to CD28 triggered the release of the cytoplasmic domain, thus making the basic residues available for binding to the effector kinase Lck and recruiting downstream components of the signaling pathway. (
  • Publications] Azuma M.: 'B70 antigen is a second ligand for CTLA-4 and CD28. (
  • CD28 antigen ligand 2. (
  • It has been shown that downmodulation of CD28 cellular surface marker expression can be obtained with engagement with its ligand 15 , prolonged stimulation with specific peptide antigens 16 , or even with cytokines such as IL-4 17 or IL-2 18 . (
  • All five potential N-linked glycosylation sites are conserved and six of the seven cysteine residues of the mouse protein are found in the human CD28 polypeptide. (
  • NY-ESO-1 or Fibroblast activation protein (FAP) linked to CD28-CD3ζ T cell signaling domains. (
  • Mutation of the basic clusters in the CD28 cytoplasmic domain reduced the recruitment to the CD28-Lck complex of protein kinase Cθ (PKCθ), which serves as a key effector kinase in the CD28 signaling pathway. (
  • Their research confirmed that IL-21 activates STAT3, a protein that then connects with the promoter region of the gene encoding the T cell stimulatory protein CD28, firing up CD28. (
  • Several antigens, in particular Chlamydia pneumoniae , human cytomegalovirus (HCMV), oxidized LDL (ox-LDL), and human heat-shock protein-60 (hHSP60), have been implicated in the pathogenesis of coronary artery disease. (
  • This protein is homologous to the CD28/CTLA-4 proteins. (
  • These results demonstrate that the CD28 signaling pathway could be activated by B7, resulting in increased T cell cytokine production and T cell proliferation. (
  • The antigens that bind to MHC proteins are always short peptides , 8-10 amino acids long for MHC Class I, and up to 25 or so for MHC Class II. (
  • CD28 also contains two proline-rich motifs that are able to bind SH3-containing proteins. (
  • Both Itk and Lck are able to phosphorylate the tyrosine residues which then allow binding of SH2 containing proteins to CD28. (
  • Its major advantages are lack of integration into the genome, transient expression of the encoded proteins, and absence of interfering immunodominant viral antigens. (
  • Although stimulation via CD28 alone usually cannot induce effector functions, its signaling pathways involve site-specific tyrosine phosphorylation of several effector proteins that are crucial for these functions ( 52 ). (
  • This review discusses the mechanisms and potential therapeutic applications of antigen-specific T cell tolerance techniques using syngeneic apoptotic cellular carriers and synthetic nanoparticles that are covalently cross-linked to diabetogenic peptides or proteins through ethylene carbodiimide (ECDI) to prevent and treat T1D. (
  • CD28 has been reported to bind to phosphatidylinositol 3-kinase (PI3-K), adaptors Grb-2/GADS, and the phosphatase PP2A ( 6 - 11 ), while CTLA-4 binds to PI3-K and phosphatases PP2A and SHP-2 ( 11 - 14 ). (
  • Phosphorylation of a tyrosine within the PYAP motif (Y191 in the mature human CD28) forms a high affinity-binding site for the SH2 domain of the src kinase Lck which in turn binds to the serine kinase PKC-θ. (
  • The past years have witnessed significant advance in our understanding of critical roles of T cell co-signals in B7-CD28 family molecules in regulating T cell activation and tolerance. (
  • 1991) CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location. (
  • CD28 co-stimulation provided by a CD28-CD3ζ CAR is important for T cell activation and persistence mediated by IL-2 secretion. (
  • Thus, we conclude that Lck signaling mediated by CD28 co-stimulation is important to promote the survival by antigen-specific IL-2 secretion. (
  • T cell clones encountering nominal antigen/MHC complexes in the absence of appropriate co-stimulation are functionally inactivated. (
  • Liu, Y., B. Jones, W. Brady, and C.A. Janeway,Jr. Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat-stable antigen. (
  • 4-8 Persistence of these antigens is considered instrumental in the initiation of inflammatory responses within the coronary arteries via activation of either macrophages or humoral and T cell-mediated response to stimulation. (
  • however, the term "antigen-presenting cell" is often used specifically to describe professional APCs. (
  • Further, the reversal of the CTLA-4 block with CD3/CD28 ligation was accompanied by an increase in surface raft expression and associated LAT. (
  • In this context, CD28 coengagement can induce raft expression under conditions where TcR ligation failed to achieve this event, and has been reported to promote the colocalization of rafts with TcR complexes ( 24 ). (
  • CD28 ligation by B7-1 or B7-2 helps in bringing the T-Cell and Antigen Presenting Cell membranes into close proximity. (
  • CD28 has also been found to stimulate eosinophil granulocytes where its ligation with anti-CD28 leads to the release of IL-2, IL4, IL-13 and IFN-γ. (
  • CD28 enhances the expression of downstream regulators that impact on T-cell proliferation, death, differentiation, and effector functions. (
  • Signaling through CD28 promotes cytokine IL-2 mRNA production and entry into the cell cycle, T-cell survival, T-helper cell differentiation and immunoglobulin isotype switching. (
  • Furthermore, inhibition of Lck signaling impaired antigen-specific IFN-γ secretion in both CAR constructs. (
  • T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. (
  • This gene segment is called CD28. (
  • As compared with gene transfer by viral or plasmid DNA, naked antigen-encoding RNA is considered a safer and superior pharmaceutical. (
  • By DNase I hypersensitivity analysis, we have identified a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb 5′ of the IL-2Rα gene. (
  • The T-cell-specific, CD28-responsive expression of the IL-2Rα gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors. (
  • CD28 has been demonstrated to play an important role in augmenting T cell proliferation and effector function. (
  • Generation of human monoclonal antibodies reactive with cellular antigens. (
  • a ) CD64-transduced K562 aAPCs were incubated with anti-CD3 and anti-CD28 monoclonal antibodies (mAbs) at the indicated concentrations and then washed. (
  • Splenocytes from BALB/c mice were stained with CD28 antibodies or with the corresponding REA Control antibodies (left image) as well as with CD3ε antibodies. (
  • Cancer vaccines that induce potent protective and therapeutic T-cell immunity against defined antigens are under active investigation. (
  • Experimental models have demonstrated that intravenous injection of autoantigen decorated splenocytes and biodegradable nanoparticles through ECDI fixation effectively induce and maintain antigen-specific T cell abortive activation and anergy by T cell intrinsic and extrinsic mechanisms. (
  • Peripheral blood T cell subsets were longitudinally evaluated by flow cytometry through the analysis of CD28, CD45RA, and CCR7 expression in 16 patients with RA who were treated with abatacept. (
  • The murine homologue of the T lymphocyte antigen CD28. (
  • T lymphocyte co-signaling pathways of the B7-CD28 family. (
  • CD28 and CD45 activate Lck which in turn induces the phosphorylation and activation of the TCR-CD3 complex and consequently, the tyrosine kinases Fyn and ZAP70. (
  • Here we show that in comparison with other application routes, intranodal vaccination using naked antigen-encoding RNA generated by in vitro transcription induces stronger biologically relevant T-cell responses and superior antitumor immunity due to the bioavailability of RNA in the lymph node and RNA inherent adjuvant effects on the lymph node microenvironment. (
  • The registered numbers of clinical trials increase annually, and a range of tumor antigens, including CEA, mesothelin, HER2, and GD2, are being targeted for various solid tumors. (
  • Patients with B cell lymphomas were simultaneously infused with 2 autologous T cell products expressing CARs with the same specificity for the CD19 antigen, present on most B cell malignancies. (
  • Antigen presentation allows for specificity of adaptive immunity and can contribute to immune responses against both intracellular and extracellular pathogens. (
  • The anti-FAP CAR recognizes surface FAP antigen while the anti-NY-ESO-1 CAR recognizes the NY-ESO-1 157-165 peptide bound to HLA-A2 on tumor cell. (
  • KLH-conjugated synthetic peptide encompassing a sequence within the N-term region of human CD28. (
  • Clone 2-4 (NB100-65334) was originally reported to recognize avian CD2, but has subsequently been found to recognize the 40kDa chicken CD28 homologue (2). (
  • However, when the individual immunosenescence markers were grouped by pathways or functional terms, several shared biological functions were identified: antigen processing and presentation pathways, MAPK, mTOR, TCR, BCR, and calcium signaling pathways, as well as key cellular metabolic, proliferation and survival activities. (
  • this process is known as antigen presentation. (
  • We have used a portion of the human CD28 cDNA to isolate a homologous murine cDNA from an EL4 T lymphoma library. (
  • Human CD28 antigen is a 44 kDa disulfide linked homodimeric T cell specific surface glycoprotein. (
  • Recombinant fragment corresponding to Human CD28. (
  • Recognizes Phospho-CD28 (Y218) from Human, Mouse. (
  • Nucleic acids are particularly attractive as they can be engineered to deliver complete antigens with optimized properties for human leukocyte antigen (HLA)-independent antigen-specific immunization ( 1 ). (
  • This signaling complex was further stabilized by the Lck-mediated phosphorylation of CD28 Tyr 207 and the subsequent binding of the Src homology 2 (SH2) domain of Lck to this phosphorylated tyrosine. (
  • We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization. (
  • Interestingly, these antigens preferentially curtailed TCR-triggered early downstream signalling events like p38 phosphorylation whereas potentiated that of Erk1/2. (
  • T-cell-specific surface glycoprotein CD28 (CD28) is involved in T-cell activation, the induction of cell proliferation, and cytokine production and promotion of T-cell survival. (
  • Complete T-cell activation requires antigen-mediated signaling through the TCR-CD3 complex and costimulatory signals that can be provided by CD28 and its counterreceptor, B7. (
  • The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. (
  • The B7-CD28 signaling pathways synergize with mitogenic signal from the TCR-CD3 complex to promote prolonged T-cell proliferation and increase interleukin-2 (IL-2) secretion ( 27 , 33 , 36 ). (
  • CD28 is a 44 kD disulfide-linked homodimeric type I glycoprotein. (
  • used fluorescence-based techniques to show that positively charged (basic) amino acids in the cytoplasmic domain of CD28 mediated its interaction with the negatively charged inner leaflet of the plasma membrane. (
  • These basic regions of CD28 have dual function, maintaining inactivity by membrane interaction and promoting activity by binding to Lck. (
  • These same clusters of basic residues also served as interaction sites for Lck, a Src family kinase critical for CD28 function. (
  • Association of the TCR of a naive T cell with MHC:antigen complex without CD28:B7 interaction results in a T cell that is anergic. (
  • antigen complex without CD28:B7 interaction results in a T cell that is anergic . (
  • 5 , 6 Therefore, one of the fundamental aspects of B-cell responses to antigen challenge that may be critical in vivo is the provision of metabolic substrates to provide ATP and anabolic precursors for cellular growth. (
  • Taken together, these data provide strong support that we have identified the murine homologue of CD28. (
  • Although CD28 can promote TcR/raft colocalization, evidence is lacking on whether the surface expression of membrane rafts can be targeted by CTLA-4 in its modulation of T cell responses. (
  • In this study, we demonstrate that both CD28 and CTLA-4 profoundly alter the surface expression of membrane rafts during T cell activation. (
  • Membrane binding by the CD28 cytoplasmic domain required two clusters of basic amino acid residues, which interacted with the negatively charged inner leaflet of the plasma membrane. (
  • CD28 and CTLA-4 have opposing effects with the coreceptors providing positive and negative signals, respectively ( 3 , 4 ). (