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 (https://immport.niaid.nih.gov/immportWeb/clinical/study/displayStudyDetails.do?itemList=SDY67). 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 2.7.11.13) - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at Researchmoz.us
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Un metodo per espandere γδ cellule T dalle cellule mononucleate del sangue periferico (PBMC) è descritta. PBMC cellule derivate γδ T...
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。
CD40山羊多克隆抗体(ab10959)可与小鼠样本反应并经WB, ELISA实验严格验证,被4篇文献引用。所有产品均提供质保服务,中国75%以上现货。
The latter can interact with CD28 on the surface of a CD4+ T cell. The dendritic cell is then a fully mature professional APC. ... An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex ( ... Antigen: protease degradation on YouTube - PMAP animation Antigen-Presenting+Cells at the US National Library of Medicine ... Professional antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to helper T ...
Mouse CD Antigen Chart Human CD Antigen Chart Human CD28 genome location and CD28 gene details page in the UCSC Genome Browser ... Some antigen-experienced T cells lose CD28 and subsequently can be re-activated without CD28 engagement. These CD28− T cells ... antigen complex without CD28:B7 interaction results in a T cell that is anergic. Furthermore, CD28 was also identified on bone ... "T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1". Proceedings of the National ...
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 for CD28 and 0.42 μM for CTLA-4), ... Neutrophils can also activate macrophages with CD80 via CD28. Last but not least, the interaction of CD80 and CD28 enhances ... 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 ...
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: ...
Another two stimulatory checkpoint molecules belong 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 ... T cells move on quickly from antigens that do not trigger responses, rapidly scanning pMHC on an antigen-presenting cell (APC) ...
"Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation". J. ...
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, which reside on the surface of cortical ...
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 ...
To prevent CD28 interaction with the CD80/CD86 receptors, these drugs modulate by binding to these receptors on antigen ... inhibition of T cell activation as well as the selective blocking of the interaction between CD80 and CD86 receptors to CD28. ...
CTLA-4 is a surface molecule present on Tregs which can prevent CD28 mediated costimulation of T cells after TCR antigen ... Antigen-loaded iDCs migrate to the lymph nodes, secrete IL-10, TGF-β and present antigen to the naive T cells without ... On the other hand, LECs can serve as a self-antigen reservoir and can transport self-antigens to DCs to direct self-peptide- ... T-cells can be made non-responsive to antigens presented if the T-cell engages an MHC molecule on an antigen presenting cell ( ...
... 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 ... CTLA-4 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 ...
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): ...
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 ...
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 ...
Huff WX, Kwon JH, Henriquez M, Fetcko K, Dey M (June 2019). "The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer ... Natural killer (NK) cell cytotoxicity and the antigen-presenting function of dendritic cells diminishes with age. The age- ... Hakim FT, Gress RE (September 2007). "Immunosenescence: deficits in adaptive immunity in the elderly". Tissue Antigens. 70 (3 ... specific for the most rare and less frequently present antigens shed the most. However, such a distribution shift leads to ...
Every helper T-cell is specific to one particular antigen. Only professional antigen-presenting cells (APCs: macrophages, B ... An example of this includes the interaction of the membrane proteins of the B7 family of the dendritic cell with CD28 present ... Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They ... Here they act as antigen-presenting cells: they activate helper T-cells and killer T-cells as well as B-cells by presenting ...
... and PD-1 has been shown to be over expressed on tumor antigen-specific (TA-specific) CD8+ T cells and CD8+ tumor ... April 2011). "Vstm3 is a member of the CD28 family and an important modulator of T-cell function". European Journal of ... "TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients". J Clin Invest. 125 (5): 2046-2058. doi:10.1172 ... T cell receptor Antigen GRCh38: Ensembl release 89: ENSG00000181847 - Ensembl, May 2017 GRCm38: Ensembl release 89: ...
Li HL, Davis W, Puré E (April 1999). "Suboptimal cross-linking of antigen receptor induces Syk-dependent activation of p70S6 ... Similar findings have been reported for NK cell receptors, CD28 family receptors, Dectin-1. Phosphorylated tyrosine residues in ... Isakov N (January 1997). "Immunoreceptor tyrosine-based activation motif (ITAM), a unique module linking antigen and Fc ... June 2010). "Constitutively active Lck kinase in T cells drives antigen receptor signal transduction". Immunity. 32 (6): 766-77 ...
The TCR/peptide-MHC complex, formed when a T cell recognises its ligand on an antigen presenting cell (APC) and the T-cell-APC ... In the resting T-cell there is no net phosphorylation of CD28 (one of the molecules providing co-stimulatory signals required ... This results in the formation of close contact zones between the membranes of the T cell and antigen presenting cell (~15 nm ... Its might also be applicable to other receptors of the Non-catalytic tyrosine-phosphorylated receptors family such as CD28. On ...
Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens (and can ... SAg stimulation of antigen presenting cells and T-cells elicits a response that is mainly inflammatory, focused on the action ... Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body's T-cells are activated, these SAgs are ... This occurs because a cognate antigen activates a T cell not because of its structure per se, but because its affinity allows ...
Thus when an antigen is properly presented to the T lymphocytes by an antigen presenting cell (APC), which displays the antigen ... Additionally, during full T-cell stimulation a costimulatory receptor CD28 activates PI3K or other pathways that eventually ... However, when T cells interacts with an antigen not presented by the APCs, that is very probably not the antigen that an immune ... usually a self-antigen. Lymphocytes are said to be anergic when they fail to respond to their specific antigen. Anergy is one ...
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 ... The process as a whole result in an effector cell, typically a T-cell, that can recognize a tumor cell antigen in a manner that ...
... antigen is a protein that in humans is encoded by the CD160 gene. CD160 is a 27 kDa glycoprotein which was initially ... CD28-CD27-cells. In tissues, CD160 is expressed on all intestinal intraepithelial lymphocytes. CD160 shows a broad specificity ... CD160+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) Human CD160 genome location and CD160 gene ... acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 ...
... is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome ... and CD28 by distinct pathways that share common elements". Journal of Virology. 85 (14): 6867-81. doi:10.1128/JVI.00229-11. PMC ... HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC ... This process can happen as quickly as 5 minutes after initial foreign antigen presentation, although typically it takes several ...
In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. The binding of PD-L1 to the ... is intermediate between its affinity for CD28 and CTLA-4 (4.0 µM and 400 nM, respectively). The related molecule PD-L2 has no ... Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or ... monocytogenes antigen-specific CD8 T cells (but not CD4 T cells). This evidence suggests that PD-L1 acts as a positive ...
GITR signaling lowers the threshold for CD28 signaling on CD8+ T cells or induces expression of CD137 on CD8+ memory T cells. ... GITR interacts with its ligand (GITRL) that is expressed on antigen-presenting cells (APC) and endothelial cells. Human ...
... antigen presentation by mouse fibroblast and hamster B-cell lines », Cell, 36, 1984, p. 319-327 Gabert, J. et al., « ... The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of ... which are responsible for capturing and presenting T cell antigens particularly effectively - present in tissues such as skin ...
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 ... 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 ... Sadelain is a recognized leader in the conceptualization and design of synthetic receptors for antigen, which he named chimeric ...
de la Fuente MA, Pizcueta P, Nadal M, Bosch J, Engel P (September 1997). "CD84 leukocyte antigen is a new member of the Ig ... The transmembrane domain of membrane-bound CD83 stabilizes MHC II, costimulatory molecules and CD28 in the membrane by ... and antigen-specific T cell responses". Journal of Immunology. 168 (1): 197-206. doi:10.4049/jimmunol.168.1.197. PMID 11751963 ... "Soluble CD83 alleviates experimental allergic rhinitis through modulating antigen-specific Th2 cell property". International ...
Specific CD8+ T cells are generated in secondary lymphoid organs where naïve T cells encounter with cytomegalovirus antigen on ... They do not express costimulatory molecules (CD28) and PD-1 receptor inhibitors on the surface, but they express the inhibitory ... antigen presenting cells. This results in a population of migrating effector CD8 + T-lymphocytes and the second small ...
... is required in addition to the antigen-specific signal from their antigen receptors. T cells require two signals ... One of the best characterized co-stimulatory molecules expressed by T cells is CD28, which interacts with CD80 (B7.1) and CD86 ... B cell binds antigens with its BCR (a membrane-bound antibody), which transfers intracellular signals to the B cell as well as ... This additional binding makes the B cells 100- to 10,000-fold more sensitive to antigen. CR2 on mature B cells forms a complex ...
Unlike MEITL, the T cells in this disease exhibit genetic abnormalities in TET2, IDH2, DNMT3A, RHOA, CD28, and VAV1 genes but ... and T-cell intracellular antigen-1) but no genetic abnormalities. Indolent T cell lymphoproliferative disorder of the ...
Identification of good antigens has been challenging: such antigens must be highly expressed on the majority of cancer cells, ... Third generation CARs combine multiple co-stimulatory domains, such as CD28-41BB or CD28-OX40, to augment T cell activity. ... After an antigen is bound to the external antigen recognition domain, CAR receptors cluster together and transmit an activation ... T cells are genetically engineered to express chimeric antigen receptors specifically directed toward antigens on a patient's ...
In order for T cells to be activated and attack an antigen, that antigen must be presented to the T cell by an APC. That ... For signal 2, the APC must present a B7 protein (CD80 or CD86) on its cell surface to a CD28 protein on the surface of the T ... One of those signals is the major histocompatibility complex (MHC), combined with the antigen, and the other signal is the CD80 ... Abatacept is a soluble CTLA-4 analog that prevents antigen-presenting cells (APCs) from delivering the co-stimulatory signal. ...
... medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28 ...
The Digital Ageing Atlas, the portal of ageing related changes
The antigens most commonly used include mumps (1 mg/mL), although availability of this antigen has varied; trichophytin (1:30 ... These molecules include CD3, CD2, CD28, and CD43.. T-cell activity can be directly studied. T lymphocytes express certain ... An assessment of functional antibody production in response to natural antigens or antigens to which the population is commonly ... Another class of stimulators includes antigens. PPD, streptokinase, Candida antigen, and tetanus toxoid all activate ...
Gene: [03q21/CD86] CD86 antigen (CD28 antigen ligand 2, B7-2 antigen); antigen CD28 ligand 2 (T lymphocyte activation antigen ... Gene: [03q21/CD80] CD80 antigen (CD28 antigen ligand 1, B7-1 antigen); antigen CD28 ligand 1 (T lymphocyte activation antigen ... CD86; antigen B7-2); [CD28LG2 ]. REL. GEM:02q33/CD28. REF. CLO,SEQ "Azuma M &: Nature, 366, 76-79, 1993. FUN "Chen C &: J ...
T-Cell Antigen CD28 Mediates Adhesion with B Cells by Interacting with Activation Anti ... Pillars Article: T-Cell Antigen CD28 Mediates Adhesion with B Cells by Interacting with Activation Antigen B7/BB-1. 1990. Proc ... T-Cell Antigen CD28 Mediates Adhesion with B Cells by Interacting with Activation Antigen B7/BB-1. 1990. Proc. Natl. Acad. Sci ...
Dive into the research topics of Aberrant Lck signal via CD28 Costimulation augments antigen-specific functionality and tumor ... Aberrant Lck signal via CD28 Costimulation augments antigen-specific functionality and tumor control by redirected T cells with ... Aberrant Lck signal via CD28 Costimulation augments antigen-specific functionality and tumor control by redirected T cells with ... Aberrant Lck signal via CD28 Costimulation augments antigen-specific functionality and tumor control by redirected T cells with ...
CD4,sup ,+,/sup,CD28,sup ,null,/sup, and CD4,sup ,+,/sup,CD28,sup ,+,/sup, cells were sorted by flowcytometry and antigen ... No antigen-specific response was noted in HC. ,i ,Conclusion,/i,. These data show that CD4,sup ,+,/sup,CD28,sup ,null,/sup, ... CD28,sup ,+,/sup, subset, but this was much weaker than that seen in the CD4,sup ,+,/sup,CD28,sup ,null,/sup, population (,svg ... After incubation with HSP60 and HSP70, CD4,sup ,+,/sup,CD28,sup ,null,/sup, cells showed increased expression at mRNA (,svg ...
PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen concentrations, PD-L2-PD-1 interactions ... PD-L expression was up-regulated on antigen-presenting cells by interferon γ treatment and was also present on some normal ... At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen ... Figure 5: Inhibition of TCR- and CD28-mediated responses by PD-L2-PD-1 and PD-L1-PD-1 interaction.. ...
... induced by antigen specific or CD3 (0.5 μg/mL) and CD28 (5 μg/mL) antibodies stimulation was evaluated by 3H-thymidine ... in addition to antigen-specific tolerance, inhibited nonspecific T-cell response to CD3/CD28 antibodies (Fig. 2A and B). We ... Thus, antigen-specific CD4+ T cells, but not CD8+ T cells, were able to convert MDSCs to nonspecific suppressor cells in vitro ... Unexpectedly, antigen-specific CD4+ T cells (but not CD8+ T cells) could dramatically enhance the immune suppressive activity ...
Engagement of CD80/86 on the antigen presenting cell with CD28 on the T cell delivers a costimulatory signal necessary for ... Antigen (or autoantigen) engages a B cell receptor directly and also is endocytosed by an antigen presenting cell (typically a ... These include (a) an antigen (or autoantigen); (b) a response by interacting families and subsets of cells that include antigen ... on activated T lymphocytes as an alternative to the CD28 ligand. When CD80/86 on the antigen presenting cell interacts with ...
Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and ... T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an ... For example, blocking stimulatory CD28 with anti-CD28 antibodies promotes regulatory T cell function and represses activation ... Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4). Cytotoxic T-lymphocyte antigen-4 (CTLA-4, CD152) inhibits early stages of T cell ...
Monoclonal antibody; inhibits T-cell CD28 activation and proliferation by binding costimulatory ligands (CD80, CD86) of antigen ... patients are defined as having evidence of acquired immunity shown by the presence of IgG antibodies to viral capsid antigen ( ... VCA) and EBV nuclear antigen (EBNA). *Epstein-Barr virus serology should be ascertained before starting administration of ...
Antigen Preparation. We prepared antigens in accordance with published methods, unless otherwise stated (17,18). For IHA, we ... containing a final concentration of 1 μL/mL anti-human CD28 and CD49d (Becton Dickinson, https://www.bd.com), along with B. ... We prepared B. thailandensis and BTCV antigens following a traditional IHA antigen preparation as described previously (17). ... and BTCV antigens as described previously (13). In brief, we added PBMC at a density of 2 × 105 cells per well to each of 2 ...
Immunologic tolerance is a state of immune unresponsiveness specific to a particular antigen or set of antigens induced by ... previous exposure to that antigen or set. Tolerance is generally accepted to be an active process and, in essence, a learning ... CD28 is the main costimulatory ligand expressed by naïve T cells encountering an antigen. Signaling by means of CD28 enhances T ... Sequestration of antigens into privileged sites. Some antigens are sequestered into privileged sites away from the immune ...
Cynarin blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells. Cynarin triggers Nrf2 ... Cynarin blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells. Cynarin triggers Nrf2 ...
Host DC will be pulsed with donor antigen to assure indirect presentation of these antigens. Thus generated DC will then be co- ... Boise, L. H., Minn, A. J., Noel, P. J., June, C. H., Accavitti, M. A., Lindsten, T., and Thompson, C. B. (1995). CD28 ... Indeed, if Treg activation is antigen specific, these cells exert their suppressor effector function in a non-antigen-specific- ... the mechanisms involved in the maintenance of tolerance to self antigens also appear required for tolerance to donor antigens ( ...
... manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 ... Background: Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with ... T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 ...
After antigen encounter and TCR activation, they also express CD40L, and thus are able to provide B cells with both of the ... IL-4 produced in response to the synergistic TCR and CD28 signals binds to IL-4R (signal 1), which, in conjunction with CD40 ... Antigen presentation by B cells favors Th2 responses. The local production of IL-4 in the bronchial mucosa by multiple cell ... Antigen presentation in the asthmatic lung: initiation of Th2 responses in the atopic bronchial mucosa.. Superimposed upon the ...
Although T cell activation can result from T cell antigen receptor (TCR) signals alone, physiological T cell responses require ... TCR-CD28 engagement at the immune synapse resulted in the colocalization of CD28 with both wild-type and mutant Rltpr forms. ... TCR-CD28 engagement at the immune synapse resulted in the colocalization of CD28 with both wild-type and mutant Rltpr forms. ... TCR-CD28 engagement at the immune synapse resulted in the colocalization of CD28 with both wild-type and mutant Rltpr forms. ...
... it may bring benefit to patients with low antigen levels (e.g., low TMB), low inflammation (e.g., low PDL-1) and/or sub-par co- ... stimulation (e.g., low CD28).. HotSpots Smart Allostery™ approach offers a diversity of advantages in delivering highly ...
CD28 is a 44 kD disulfide-linked homodimeric type I glycoprotein. ... Antigen Details Structure Ig superfamily, type I transmembrane ... In vitro studies indicate that ligation of CD28 on T cells by CD80 and CD86 on antigen presenting cells provides a ... CD28 is expressed on most T lineage cells, NK cell subsets, and plasma cells. CD28 binds both CD80 and CD86 using a highly ... Antigen References 1. Schlossman S, et al. Eds. 1995. Leucocyte Typing V. Oxford University Press. New York.. 2. June CH, et al ...
... tumor antigens, self-antigens) to CD8 T cells. The class II molecules present extracellular antigens such as extracellular ... NK cells also provide help to CD28-positive host T cells, thereby promoting allograft rejection. [10] Their importance in the ... Other antigens cause only weaker reactions, but combinations of several minor antigens can elicit strong rejection responses. ... The antigens responsible for rejection of genetically disparate tissues are called histocompatibility antigens; they are ...
Therefore, a second-generation CAR was utilised, bearing CD3zeta and CD28 co-stimulatory domains, as successfully used in ... Eine hohe Effizienz zeigte sich auch während der Kultivierung mit antigen-negativen Zellen, denen antigen-positive Zielzellen ... DARPin-targeted Chimeric Antigen Receptor T cells: CD4 as a cellular target shows potential to evade HIV latency reservoir ... DARPin-targeted Chimeric Antigen Receptor T cells: CD4 as a cellular target shows potential to evade HIV latency reservoir.. ...
E5.478.594.49 Antigens, CD147 D12.776.543.550.188 D12.776.543.550.187 Antigens, CD28 D12.776.543.750.705.816.824.133 D12.776. ... 543.750.705.222.500 Antigens, CD70 D12.776.543.550.172 D12.776.543.550.170 Antigens, CD8 D23.50.301.264.35.108 Antigens, CD80 ... D23.529.168.100 Antigens, CD86 D12.776.395.550.17 D12.776.467.150.200 D12.776.543.550.186 D12.776.543.95.200 D23.50.301.264. ... A1.923.47.365 H-2 Antigens D23.50.301.500.400.350 D23.50.301.500.100.350 D23.50.705.552.400.350 D23.50.301.500.400.199 D23.50. ...
Dual-antigen receptor: CAR T cells are engineered to express two tumor-associated antigen receptors at the same time, reducing ... such as CD28-41BB or CD28-OX40, to augment T cell activity. Preclinical data show the third-generation CARs exhibit improved ... Chimeric antigen receptor structureEdit. Chimeric antigen receptors combine many facets of normal T cell activation into a ... Antigen recognition domainEdit. The antigen recognition domain is exposed to the outside of the cell, in the ectodomain portion ...
When the T-cell receptor (TCR) binds to antigen and major histocompatibility complex (MHC) proteins on the APC and CD28 binds ... Checkpoint proteins, such as B7-1/B7-2 on antigen-presenting cells (APC) and CTLA-4 on T cells, help keep the bodys immune ...
Testi R, Lanier LL (1989) Functional expression of CD28 on T cell antigen receptor γ/δ-bearing T lymphocytes. Eur J Immunol 19( ... we chose immobilized anti-CD28 mAb for reasons of comparison with anti-CD3/anti-CD28 bead stimulation [50]. To omit CD28 ... CD28 stimulation is not essential for Vδ2+ T cell suppression of autologous αβ T cells. Peters et al. suggested that CD28 ... exert their suppressive function only in the presence of anti-CD28 stimulation or antigen-presenting cells and that anti-CD28 ...
A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28 antibodies enables rapid expansion and long-term ... Several CAR constructs containing a CD28 intracellular signaling domain provoke antigen-independent T cell activation and ... T cells were stimulated with anti-CD3/CD28 beads or artificial antigen-presenting cells that express a membrane-bound form of ... anti-CD3/CD28 Dynabeads or anti-CD3/CD28/CD137 Dynabeads (Thermo Fisher Scientific) at a bead/T cell ratio of 1:1 according to ...
D) Representative FACS histograms of Pros1 expression on resting and activated CD4+ T cells with anti-CD3/CD28 for 15 h. Gray ... the professional antigen presenting cells, drives T cell activation. These essential functions notwithstanding, the Itga4 ... C) Splenic CD4+ cells were isolated and activated with anti-CD3/CD28. mRNA expression was determined by qPCR and normalized to ... direct activation of isolated murine splenic CD4+ T cells via anti-CD3 and anti-CD28 stimulation led to the up-regulation of ...
T cells were activated with Transact CD3 CD28 reagent in the presence of IL-2, and transduced with LV as described in Methods. ... Creation of Chimeric Antigen Receptor (CAR) - expressing vectors. CAR antigen-binding domains, scFv, sequences were derived ... This may indicate that both antigen-specific and non-antigen-specific mechanisms of escape are possible in the Raji cell ... To target hematologic malignancies with a chimeric antigen receptor (CAR) that targets two antigens with a single vector, and ...

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