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).

Identification of CD137 as a potent monocyte survival factor. (1/282)

CD137 (ILA/4-1BB), a member of the tumor necrosis factor (TNF) receptor family, promotes adherence and prolongs survival of human peripheral monocytes. It induces a strong expression of macrophage colony-stimulating factor (M-CSF), an essential monocyte survival factor. Monocyte survival induced by CD137 is primarily mediated by M-CSF and to a lesser extent by granulocyte-macrophage colony-stimulating factor and IL-3. Survival and induction of M-CSF are mediated via reverse signaling through a CD137 ligand expressed constitutively by peripheral monocytes.  (+info)

CD137-induced apoptosis is independent of CD95. (2/282)

CD95 (APO-1/Fas) and CD137 (ILA/4-1BB) are members of the tumour necrosis factor receptor family, and both are involved in induction of apoptosis in lymphocytes. Contrary to the case of CD95, apoptosis by CD137 is caused by cross-linking of the respective ligand rather than the receptor. Nothing is known so far about the mechanism of CD137-induced cell death. Here, we show that immobilized CD137 protein induces expression of CD95 in resting primary T and B lymphocytes. However, induction of apoptosis by CD137 is independent of CD95, because: (1) antagonistic anti-CD95 antibody fragments do not block CD137-induced apoptosis; and (2) CD137, but not anti-CD95, can induce apoptosis in resting lymphocytes.  (+info)

Role of the stress kinase pathway in signaling via the T cell costimulatory receptor 4-1BB. (3/282)

4-1BB is a member of the TNFR superfamily expressed on activated CD4+ and CD8+ T cells. 4-1BB can costimulate IL-2 production by resting primary T cells independently of CD28 ligation. In this study, we report signaling events following 4-1BB receptor aggregation using an Ak-restricted costimulation-dependent T cell hybridoma, C8.A3. Aggregation of 4-1BB on the surface of C8.A3 cells induces TNFR-associated factor 2 recruitment, which in turn recruits and activates apoptosis signal-regulating kinase-1, leading to downstream activation of c-Jun N-terminal/stress-activated protein kinases (JNK/SAPK). 4-1BB ligation also enhances anti-CD3-induced JNK/SAPK activation in primary T cells. Overexpression of a catalytically inactive form of apoptosis signal-regulating kinase-1 in C8.A3 T cells interferes with activation of the SAPK cascade and with IL-2 secretion, consistent with a critical role for JNK/SAPK activation in 4-1BB-dependent IL-2 production. Given the ability of both CD28 and 4-1BB to induce JNK/SAPK activation, we asked whether hyperosmotic shock, another inducer of this cascade, could function to provide a costimulatory signal to T cells. Osmotic shock of resting primary T cells in conjunction with anti-CD3 treatment was found to costimulate IL-2 production by the T cells, consistent with a pivotal role for JNK/SAPK in T cell costimulation.  (+info)

The structural basis for the recognition of diverse receptor sequences by TRAF2. (4/282)

Many members of the tumor necrosis factor receptor (TNFR) superfamily initiate intracellular signaling by recruiting TNFR-associated factors (TRAFs) through their cytoplasmic tails. TRAFs apparently recognize highly diverse receptor sequences. Crystal structures of the TRAF domain of human TRAF2 in complex with peptides from the TNFR family members CD40, CD30, Ox40, 4-1BB, and the EBV oncoprotein LMP1 revealed a conserved binding mode. A major TRAF2-binding consensus sequence, (P/S/A/T)x(Q/E)E, and a minor consensus motif, PxQxxD, can be defined from the structural analysis, which encompass all known TRAF2-binding sequences. The structural information provides a template for the further dissection of receptor binding specificity of TRAF2 and for the understanding of the complexity of TRAF-mediated signal transduction.  (+info)

CD137 induces proliferation and endomitosis in monocytes. (5/282)

Peripheral monocytes are short-lived and are replenished from hematopoietic stem cells whose proliferation is believed to be confined to the bone marrow. Human peripheral monocytes are assumed not to be able to proliferate. In this study we show that CD137 (ILA/4-1BB), a member of the tumor necrosis factor receptor family, induces a widespread and profound proliferation of human peripheral monocytes. Macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor are essential, but not sufficient for proliferation. Additional soluble autocrine factors induced by CD137 are required. Induction of proliferation is mediated via reverse signaling through a CD137 ligand, expressed constitutively by peripheral monocytes. The ability of CD137 to induce proliferation in human peripheral monocytes is not shared by any other known molecule.  (+info)

Anti-4-1BB monoclonal antibodies abrogate T cell-dependent humoral immune responses in vivo through the induction of helper T cell anergy. (6/282)

The 4-1BB receptor (CDw137), a member of the tumor necrosis factor receptor superfamily, has been shown to costimulate the activation of T cells. Here we show that anti-mouse 4-1BB monoclonal antibodies (mAbs) inhibit thymus-dependent antibody production by B cells. Injection of anti-4-1BB mAbs into mice being immunized with cellular or soluble protein antigens induced long-term anergy of antigen-specific T cells. The immune response to the type II T cell-independent antigen trinintrophenol-conjugated Ficoll, however, was not suppressed. Inhibition of humoral immunity occurred only when anti-4-1BB mAb was given within 1 wk after immunization. Anti-4-1BB inhibition was observed in mice lacking functional CD8(+) T cells, indicating that CD8(+) T cells were not required for the induction of anergy. Analysis of the requirements for the anti-4-1BB-mediated inhibition of humoral immunity revealed that suppression could not be adoptively transferred with T cells from anti-4-1BB-treated mice. Transfer of BALB/c splenic T cells from sheep red blood cell (SRBC)-immunized and anti-4-1BB-treated mice together with normal BALB/c B cells into C.B-17 severe combined immunodeficient mice failed to generate an anti-SRBC response. However, B cells from the SRBC-immunized, anti-4-1BB-treated BALB/c mice, together with normal naive T cells, exhibited a normal humoral immune response against SRBC after transfer, demonstrating that SRBC-specific B cells were left unaffected by anti-4-1BB mAbs.  (+info)

CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes. (7/282)

Human CD137 is a member of the tumor necrosis factor (TNF) receptor family and the homologue of murine 4-1BB. Recent studies have demonstrated that CD137 promotes accessory T cell activation, and regulates proliferation and survival of T lymphocytes. This study reports on the expression and function of CD137 in peripheral blood monocytes. While monocytes showed constitutive expression in 10 out of 18 healthy donors, CD137 was not expressed on resting T or B lymphocytes. Immobilized antibodies to CD137 markedly induced the production of IL-8 and TNF-alpha protein and mRNA, and led to inhibition of IL-10 expression by primary monocytes. Furthermore, cross-linking of CD137 on monocytes resulted in an increase of B lymphocyte apoptosis mediated by direct cell-cell contact of both cell populations. In conclusion, this study identified CD137 as a new receptor involved in monocyte activation by inducing a characteristic cytokine release profile. In addition, CD137 may play a role in monocyte-dependent control of B lymphocyte survival.  (+info)

4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. (8/282)

Peptide vaccination induces T cell activation and cytotoxic T cell development. In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems. 4-1BBL-deficient (-/-) and wild-type (+/+) mice were immunized with a lipidated lymphocytic choriomeningitis virus (LCMV) peptide NP396-404. Analysis of peptide-specific responses early after immunization by CTL assay, intracellular IFN-gamma staining, and IFN-gamma enzyme-linked immunospot assay (ELISPOT) indicated that CD8 T cell responses were reduced 3- to 10-fold in the absence of 4-1BB costimulation. Moreover, when agonistic anti-4-1BB Ab was given, CD8 T cell responses in 4-1BBL-/- mice were augmented to levels similar to those in 4-1BBL+/+ mice. Two months after immunization, 4-1BBL+/+ mice still had epitope-specific cells and were protected against viral challenge, demonstrating that peptide vaccination can induce long-term protection. In fact, 70% of CD8 T cells were specific for the immunizing peptide after viral challenge, demonstrating that strong, epitope-specific CD8 T cell responses are generated after peptide vaccination. In contrast, peptide-immunized 4-1BBL-/- mice had fewer epitope-specific cells and were impaired in their ability to resolve the infection. These results show that immunization with a single LCMV peptide provides long term protection against LCMV infection and point to costimulatory molecules such as 4-1BB as important components for generating protective immunity after vaccination.  (+info)

Purpose: Cultured tumor fragments from melanoma metastases have been used as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy. The expansion of tumor-reactive CD8+ T cells with IL-2 in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8+ T cells recently found to constitute the majority of tumor-specific T cells. Experimental Design:We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB co-stimulation. Results: Addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8+ TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFkappaB activation and the induction of T-cell survival and memory genes, as well as enhanced IL-2 responsiveness, in the CD8+ T cells in the fragments and emerging from the ...
The LOB12.3 monoclonal antibody reacts with mouse 4-1BB, a TNF receptor superfamily member also known as CD137. 4-1BB is a 39 kDa transmembrane protein expressed by T lymphocytes, NK cells, dendritic cells, granulocytes, and mast cells. Upon binding its ligand 4-1BBL, 4-1BB provides costimulatory signals to both CD4 and CD8 T cells through the activation of NF- κB, c-Jun and p38 downstream pathways. The importance of the 4-1BB pathway has been underscored in a number of diseases, including cancer. Agonistic anti-4-1BB antibodies have been reported to induce T cell mediated antitumor immunity. The LOB12.3 antibody is an agonistic antibody that has been shown to stimulate 4-1BB signaling and delay tumor growth |em|in vivo|/em| when administered in combination with immune checkpoint inhibitors.
Sires With Kappa Casein BB/AB & Fleckvieh/Milking-Simmentals & Cow - Besamungsunternehemen Rind Schwein Embryotransfer Managementberatung
Sires With Kappa Casein BB/AB & Fleckvieh/Milking-Simmentals & Cow - Besamungsunternehemen Rind Schwein Embryotransfer Managementberatung
I noticed some play in the BB on my Trek Cronus CX. Removed the cranks on NDS bearing but I cant remove the DS bearing. Even with the appropriate Park Tool there is not enough room behind the bearing for the bushing to sit and hit against because of a plastic sleeve which runs between the two bearings. I tried to slide the sleeve to the side but it wont budge ...
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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 ...
Description: 4-1BB Receptor, a member of the TNF superfamily of receptors, is mainly expressed on the surface of a variety of T cells, but also found in B cells, monocytes, and various transformed cell lines. 4-1BB Receptor binds to 4-1BBL to provide a co-stimulatory signal for T lymphocytes. Signaling by 4-1BB Receptor has been implicated in the antigen-presentation process and generation of cytotoxic T cells. The human 4-1BB Receptor gene codes for a 255 amino acid type I transmembrane protein containing a 17 amino acid N-terminal signal sequence, a 169 amino acid extracellular domain, a 27 amino acid transmembrane domain and a 42 amino acid cytoplasmic domain. Recombinant human soluble 4-1BB Receptor is a 167 amino acid polypeptide (17.7 kDa), which contains the cysteine rich TNFR-like extracellular domain of 4-1BB Receptor ...
Description: 4-1BB Receptor, a member of the TNF superfamily of receptors, is mainly expressed on the surface of a variety of T cells, but also found in B cells, monocytes, and various transformed cell lines. 4-1BB Receptor binds to 4-1BBL to provide a co-stimulatory signal for T lymphocytes. Signaling by 4-1BB Receptor has been implicated in the antigen-presentation process and generation of cytotoxic T cells. The human 4-1BB Receptor gene codes for a 255 amino acid type I transmembrane protein containing a 17 amino acid N-terminal signal sequence, a 169 amino acid extracellular domain, a 27 amino acid transmembrane domain and a 42 amino acid cytoplasmic domain. Recombinant human soluble 4-1BB Receptor is a 167 amino acid polypeptide (17.7 kDa), which contains the cysteine rich TNFR-like extracellular domain of 4-1BB Receptor ...
4-1BBL, a member of the TNF superfamily, is expressed in B cells, dendritic cells, activated T cells and macrophages. 4-1BBL binds to its receptor
TOPOL, Josef - NYKLOVÁ-VESELÁ, Milena: Bloudění ve vlastní duši. Hovořila Milena Nyklová. Biblio. Roč. 3 (8), 2015, č. 8, 13. 8., s. 4-7 ...
A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES ...
Example of Table 22.3. Here is the Scalogram for Example 5, a computer-adaptive, multiple-choice test. The original responses are shown.. GUTTMAN SCALOGRAM OF ORIGINAL RESPONSES:. STUDENT ,TOPIC. , 11 3 11 1 3212232212132425654421434145625 36555366356465464633654. ,640215038189677748390992315641640517264579268221076889430372139553458. ,---------------------------------------------------------------------. 3 + d b c db d c b cd S STA. 6 + c b c d d c cd S CHU. 27 + c c c c cbb a dd c b dd S ERI. 4 + c b a d cb c dd d b d dc S CHE. 9 + d c a a cbc c ba b dca c db dc bbdbb c S MEL. 25 + c b d c bc a a d a c dba d cbccbd c S DAN. 24 + a d ac b c d c b a a AP SAR. 12 + c b c c b b b b a cb cc c A ALL. 28 + c c a bcc b c acc d b bc b c bdcb d IH GRE. 21 + b c b a c b a bc bb ab a db bbd cc b b AP MIL. 11 + a d c b cc cbad d ca c d ca ba b ac bac bc d c cc S CHR. 17 + d d c c acac cac b c a a b c c bc b ac ac IH FRA. 7 + d c d ccaaac d bcd ca b cb c b a a a a ab b bb ac IH JAN. 1 + c c ab ca dc b a a c ...
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View mouse Tnfrsf18 Chr4:156026164-156028895 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
View mouse Tnfrsf13b Chr11:61126755-61149372 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
These reference sequences exist independently of genome builds. Explain. These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above. ...
Dose-limiting toxicity of cancer drugs is a main hurdle facing the development of effective treatments for cancer. Immunostimulatory drugs are no different. Ipilimumab, a monoclonal antibody that blocks the function of the coinhibitory receptor CTLA-4, is the first U.S. Food and Drug Administration-approved immunostimulatory antibody that has shown clinical benefit in patients with cancer. Nonetheless, ipilimumab treatment is associated with significant dose-dependent toxicities and grade 3 to 4 adverse effects including colitis and hypophysitis (26). Likewise, treatment with an agonistic 4-1BB antibody while showing antitumor efficacy was also associated with grade 3 or higher neutropenia and elevated liver enzymes (27), and severe hepatic toxicity at higher doses that led to the suspension of the clinical trial (27, 28). The potential toxicity of immunostimulatory antibodies was underscored by unexpected severe toxicities seen in healthy volunteers treated with a super agonistic anti-CD28 ...
Supplementary MaterialsSupp Numbers1-S6. memory space cells was T-cell-intrinsic. Therefore, c-IAP E3 activity is required for 4-1BB co-receptor signaling and maintenance of CD8+ T-cell memory space. infection due to very high effector cytokine levels produced during the main effector response [27]. Using these mice, we have EMD534085 analyzed 4-1BB signaling and both the acute and memory space response to LCMV. We find that signaling downstream 4-1BB, and consequently the maintenance of a functional and effective pool of memory space T cells, requires c-IAP E3 activity. Results Impaired 4-1BB-induced signaling in c-IAP2H570A T cells In vitro studies have shown that engagement of 4-1BB on T cells induces the activation of the canonical NF-B pathway inside a c-IAP-dependent manner [18C20, 24]. We analyzed the part of c-IAP E3 activity in this process by taking advantage of mice in which endogenous c-IAP2 has been replaced with an E3-inactive point mutant, c-IAP2H570A, that also functions as ...
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Tnfrsf1a (untagged) - Mouse tumor necrosis factor receptor superfamily, member 1a (cDNA clone MGC:6117 IMAGE:3585060), (10ug), 10 µg.
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Tumor necrosis factor receptor superfamily, member 19, also known as TNFRSF19 and TROY is a human gene. The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is highly expressed during embryonic development. It has been shown to interact with TRAF family members, and to activate JNK signaling pathway when overexpressed in cells. This receptor is capable of inducing apoptosis by a caspase-independent mechanism, and it is thought to play an essential role in embryonic development. Alternatively, spliced transcript variants encoding distinct isoforms have been described. GRCh38: Ensembl release 89: ENSG00000127863 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000060548 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: TNFRSF19 tumor necrosis factor receptor superfamily, member 19. Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, et al. (1995). Isolation of novel and known genes from a human fetal cochlear ...
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PubMed journal article: Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells. Download Prime PubMed App to iPhone, iPad, or Android
TNFRSF9 - TNFRSF9 (untagged)-Human tumor necrosis factor receptor superfamily, member 9 (TNFRSF9) available for purchase from OriGene - Your Gene Company.
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This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
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Research proven purified goat polyclonal TRAIL R3, DcR 1 or CD263 antibody. DcR1 is attached to the cell surface through glycophospholipid anchor. It has the extracellular TRAIL binding domain but lacks the cytoplasmic domain to induce apoptotic signal. Hence overexpression of DcR1 inhibits the TRAIL induced apoptosis. Designed for immunohistochemistry, western blotting, ELISA and related apllications. IHC image in product description.
The TNFRSF11A gene encodes a member of the TNF receptor family and is therefore involved in regulation of immunen processes. Mutations cause autosomal recessive juvenile Paget disease, osteopetrosis, and dominant familial expansile osteolysis.. ...
TY - JOUR. T1 - 4-1BB signaling synergizes with programmed death ligand 1 blockade to augment CD8 T cell responses during chronic viral infection. AU - Vezys, Vaiva. AU - Penaloza-Macmaster, Pablo. AU - Barber, Daniel L.. AU - Ha, Sang Jun. AU - Konieczny, Bogumila. AU - Freeman, Gordon J.. AU - Mittler, Robert S.. AU - Ahmed, Rafi. PY - 2011/8/15. Y1 - 2011/8/15. N2 - Previous studies have identified the inhibitory role that the programmed death 1 (PD-1) pathway plays during chronic infection. Blockade of this pathway results in rescue of viral-specific CD8 T cells, as well as reduction of viral loads in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). We tested the effect of combining PD ligand 1 (PD-L1) blockade with an agonistic regimen that induces 4-1BB costimulation during chronic LCMV infection. There is a boosting effect in the rescue of LCMV-specific CD8 T cell responses after dual treatment with PD-L1 blockade and 4-1BB agonistic Abs when the amount and timing ...
Glucocorticoid-induced TNFR family related protein (GITR, CD357 or TNFRSF18) is a member of the tumor necrosis factor receptor superfamily (TNFRSF). Like other T cell co-stimulatory TNFR family members, GITR utilizes multiple oligomerization states to regulate the initiation of downstream signaling during T cell activation by antigen presenting cells (APCs). The formation of receptor superclusters, comprised of two or more trimeric molecules, has been defined for multiple TNFRs as a means of regulating downstream signal amplification. For co-stimulatory TNFRs, like GITR, CD137 and OX40, signaling outcomes in T cells are primarily mediated via the NFκB pathway that promotes cell survival and effector cell activities in response to suboptimal T cell receptor (TCR) stimulation. It has been hypothesized that the manipulation of the oligomeric states of co-stimulatory TNFRs using antibodies may have therapeutic utility in enhancing the activity of tumor-reactive T cells, either as single agents or ...
Clone REA738 recognizes the human CD95 antigen, also known as Fas and Apo-1, which is a member of the tumor necrosis factor receptor superfamily (TNFR) and is found on the surface of many normal and neoplastically transformed cells. Its ligand, CD95L (FasL/Apo-1L), is able to induce apoptosis in CD95-expressing cells upon binding. CD95 and CD95L are up-regulated on lymphocytes upon activation and are known to play a key role in the regulation of an inflammatory response: Juxtocrine
CD95, also known as FAS or Apo-1, is a member of the tumor necrosis factor receptor superfamily (TNFR) and is found on the surface of many normal and neoplastically transformed cells. Its ligand, CD95L (FASL/Apo-1L), is able to induce apoptosis in CD95-expressing cells upon binding. CD95 and CD95L are up-regulated on lymphocytes upon activation and are known to play a key role in the regulation of an inflammatory response: Juxtocrine
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels ...
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Inhibitors of tumour necrosis factor (TNF) are among the most successful protein-based drugs (biologics) and have proven to be clinically efficacious at reducing inflammation associated with several autoimmune diseases. As a result, attention is focusing on the therapeutic potential of additional me …
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US High Yield BB Effective Yield historical data, charts, stats and more. US High Yield BB Effective Yield is at 4.32%, compared to 4.31% the previous market day and 4.65% last year. This is lower than the long term average of 7.19%..
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T cells based on antigen-triggered CD137 expression". Journal of Immunological Methods. 339 (1): 23-37. doi:10.1016/j.jim. ... The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T ... CD137 is expressed by activated T cells of both the CD4+ and CD8+ lineages. Although it is thought to function mainly in co- ... stimulating those cell types to support their activation by antigen presenting cells expressing its ligand (CD137L), CD137 is ...
CD137: When this molecule, also called 4-1BB, is bound by CD137 ligand, the result is T-cell proliferation. CD137-mediated ... CD27: This molecule supports antigen-specific expansion of naïve T cells and is vital for the generation of T cell memory. CD27 ... The ligand for GITR is mainly expressed on antigen presenting cells. Antibodies to GITR have been shown to promote an anti- ... CD40: This molecule, found on a variety of immune system cells including antigen presenting cells has CD40L, otherwise known as ...
Increasing the reactivity of TIL towards tumor antigen through CD137 or PD-1 is a possible direction of treatment improvement. ... 2) And therapy efficacy would be limited by antigen modulation related to antigen down-regulation and when infused back into ... Antigens presented only on the tumor, but not in the healthy tissue should be identified to decrease the chance of TCRs ... Chimeric antigen receptor T-cells (CAR-T) are predominantly used in cancer immunotherapy. T-cells are harvested from patients' ...
4-1BBL is a type 2 transmembrane glycoprotein receptor that is found on APCs (antigen presenting cells) and binds to 4-1BB ( ... CD137 GRCh38: Ensembl release 89: ENSG00000125657 - Ensembl, May 2017 "Human PubMed Reference:". National Center for ... also known as CD137). The 4-1BB/4-1BBL complex belongs to the TNFR:TNF superfamily, which is expressed on activated T ...
The CD137 presence within the cells maintains the persistence of the engineered T cells. This interaction between engineered T ... cells with CD28 and CD137 are essential for immunotherapy, and show promise for directing T lymphocytes to tumor antigens and ... Additionally, genetically engineered T cells containing CD28 and CD137 can be used in a molecularly targeted therapy response ... established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains". Proceedings of the ...
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 ... such as CD137, OX40 or CD27. GITR is constitutively expressed on CD25+CD4+ regulatory T cells and its expression is upregulated ...
A number of approaches have been considered to amplify T cell mediated immune responses(e.g. IL-2, CTLA-4, IL-7, CD137), and ... tumor-associated antigens, or whole tumor cells, can induce specific T-cell mediated immune responses. ...
Identification of good antigens has been challenging: such antigens must be highly expressed on the majority of cancer cells, ... and CD137 (4‐1BB). The intracellular signaling domain used defines the generation of a CAR T cell. First generation CARs ... 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 the TNF family of molecules, the protein 4-1BB (CD137) on the T cell may bind to 4-1BB ligand (4-1BBL) on the APC. The B7 ( ... This is also called "Signal 1" and its main purpose is to guarantee antigen specificity of the T cell activation. However, MHC ... B7 is a type of integral membrane protein found on activated antigen-presenting cells (APC) that, when paired with either a ...
Antigen CD19 appears only on B cells, which go awry in lymphoma and leukemia. Loss of B cells can be countered with ... potentially including costimulatory domains encoding CD28 or CD137. CARs can provide recognition of cell surface components not ... Cancer-testes antigen MAGE-A3 is not known to be expressed in any normal tissues. However, targeting an HLA-A*0201-restricted ... Cancer-testis antigens are a family of intracellular proteins that are expressed during fetal development, but with little ...
OX40L is the ligand for OX40 (also known as CD134 or TNFRSF4) and is stably expressed on many antigen-presenting cells such as ... December 2002). "Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), ...
An anticancer drug is coupled to an antibody that targets a specific tumor antigen (or protein) that, ideally, is only found in ... induces tumor localized CD137 agonism". J Immunother Cancer. 9 (11): e002883. doi:10.1136/jitc-2021-002883. PMID 34725211. ... Antibodies attach themselves to the antigens on the surface of cancerous cells. The biochemical reaction that occurs upon ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
CD137neg counterparts did not respond (Fig. 3B and C). CD137 upregulation was antigen-driven because CD137pos and CD137neg TILs ... and CD137negPD-1+ TIL subsets revealed a dichotomy in tumor antigen-specific reactivity. CD137posPD-1+ and CD137posPD-1neg TILs ... For specific antigen stimulation of isolated CD137pos and CD137neg T cells, 106 T2 cells were loaded with 1 μmol/L MART-1:26-35 ... CD137pos and CD137neg fractions were isolated and rested in media for 10 days. CD137pos, CD137neg, or nonmanipulated TILs were ...
... remodeling is postulated to leave CD137-costimulated T lymphocytes poised to differentially respond upon subsequent antigen ... CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously ... Accordingly, CD137 connects costimulation during priming to genome-wide DNA methylation and chromatin reprogramming. (C) 2017 ... CD69 is an early activation marker on the surface of T lymphocytes undergoing activation by cognate antigen. We observed ...
GMP-compliant flow cytometric cell sorting of antigen-specific T cells using MACS® GMP CD8-APC and MACS GMP CD137-PE ... Isolation of antigen specific CD8+ T cells using the MACSQuant® Tyto® : A closed, sterile, single use Microchip based cell ...
... a well-validated tumor antigen; and BT7480, a Bicycle TICA™ targeting Nectin-4 and stressful CD137, in company-sponsored Phase ...
Prior treatment with cluster of differentiation 137 (CD137) agonists, anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti- ...
... anti-human CD137 (4-1BB) Antibody - CDw137 is a 39 kD transmembrane protein also known as 4-1BB. ... Antigen References 1. Gruss H, et al. 1995. Blood 85:3378.. 2. Sica G, et al. 2000. Adv. Exp. Med. Biol. 465:355.. 3. Alderson ... View All CD137 Reagents Request Custom Conjugation Description. Clone. Applications. Purified anti-human CD137 (4-1BB). 4B4-1. ... CD137 is a 39 kD transmembrane protein also known as 4-1BB. It is expressed on activated T cells. CD137 is a type I membrane ...
The receptor we are engineering to be expressed on the surface of the T cell is called a chimeric antigen receptor (CAR). The ... CD137, and CD3-zeta chain) signaling domains are included in retroviral backbone vectors.9 Tumor-binding domains, with or ... In this study, we will target a known tumor antigen on the surface of sarcoma, GD2. Our hypothesis is that more tumor specific ... Figure 1: Basic Chimeric Antigen Receptor (CAR).. One limitation for using adoptive T-cell transfer for the treatment of cancer ...
Jiang J, Wang X, Wang X, Cao Z, Liu Y, Dong M, Tong A, Cheng X. Reduced CD27 expression on antigen-specific CD4+ T cells ... also known as CD137)-4-1BB ligand, CD27-CD70. To avoid over-reactivation, effector T cell response also require suppression ... BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell ... CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens. Immunity. 2015;42(3):471- ...
TCR reconstruction and antigen specificity screening was done and a CD137 upregulation assay was run to determine the TCR ... that antigens associated with melanoma demonstrated strong tumor recognition and low avidity with highly available antigens [2 ... and their antigens that allows this immune response to occur, but the connection between the phenotypic characteristics and the ... The T cell receptors specific for MAAs had lower avidity coupled with stronger tumor recognition due to an abundance of antigen ...
Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl ... and priming of the adaptive immune response via T-lymphocyte response to tumor-specific antigens.[13] Strategies to extend this ... Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of ... such as an anti-CD137 agent increasing trastuzumab-mediated natural killer cell activity,[14] TLR2 (toll-like receptor 2) ...
The dimeric antigen receptors have antibody-like properties as they bind specifically to a target antigen. The dimeric antigen ... The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. ... constructs that bind a BCMA target antigen, where the DAR construct comprises a heavy chain binding region on one polypeptide ... The present disclosure provides dimeric antigen receptors (DAR) ... CD137, CD154, LFA-1 T cell co-receptor, CD2 T cell co-receptor/ ...
... a CD137 signaling domain, and a CD3-zeta-derived signaling domain, as previously reported [13], Fig. 1. The heavy and light ... 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 ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
4-1BB Receptors use Antigens. CD137 4-Acetamido-4-isothiocyanatostilbene-2,2-disulfonic Acid ...
Antigens, CD137. 2. + 181. Argininosuccinate Synthase. 2. + 182. Integrin alpha1beta1. 2. + 183. Palladium. 2. + ...
... monoclonal antibodies recognizing tumor antigens, chemotherapy, or molecular targeted agents. Clinical phase I-II studies of IL ... Human T cells genetically engineered to express a chimeric antigen receptor (CAR) specific for the CD19 B cell antigen and ... X. Wang, D. A. Lee, Y. Wang et al., "Membrane-bound interleukin-21 and CD137 ligand induce functional human natural killer ... Indeed CD8+ T cells accumulate in Socs1−/− mice [42]. In vitro studies also showed that IL-21 inhibited the antigen-induced ...
CD137; TNFRSF9; 4-1BB ligand receptor; 41BB; 4-1BB; CDw137; FLJ43501; ILA; T cell antigen ILA ... CD Antigens. Fc Receptors. Receptor Proteins. Enzymes & Regulators. Complement System. Ubiquitin Related Proteins. Viral ... Cytokines and Growth Factors Immune Checkpoint Proteins CD Antigens Biotinylated Proteins * TNF Superfamily Stimulatory immune ...
  • Receptor-ligand interaction is required for the transduction of second signal, following the first signal conveyed by the interaction of MHC molecules on APCs and T cell receptors on effector T cells loaded with cognate antigens [ 3 ]. (
  • It is the interaction between T cell receptors (TCRs) and their antigens that allows this immune response to occur, but the connection between the phenotypic characteristics and the TCR properties is not well characterized. (
  • The T cell receptors specific for MAAs had lower avidity coupled with stronger tumor recognition due to an abundance of antigen availability. (
  • The present disclosure provides dimeric antigen receptors (DAR) constructs that bind a BCMA target antigen, where the DAR construct comprises a heavy chain binding region on one polypeptide chain and a light chain binding region on a separate polypeptide chain. (
  • The two polypeptide chains that make up the dimeric antigen receptors can dimerize to form an antigen binding domain. (
  • The dimeric antigen receptors have antibody-like properties as they bind specifically to a target antigen. (
  • The dimeric antigen receptors can be used for directed cell therapy. (
  • The present disclosure provides dimeric antigen receptors (DAR) protein constructs that bind specifically to a target antigen, nucleic acids that encode the dimeric antigen receptors, vectors comprising the nucleic acids, and host cells harboring the vectors. (
  • Chimeric antigen receptors (CARs) have been developed to target antigens associated, in particular, with cancer. (
  • Adoptive immunotherapy by infusion of T cells engineered with chimeric antigen receptors (CARs) for redirected tumoricidal activity represents a potentially highly specific modality for the treatment of metastatic cancer. (
  • Antigen receptors comprising both an antibody heavy chain binding region and an antibody light chain binding region in separate polypeptide chains and their use in directed cell therapy are disclosed herein in an effort to meet this need and/or provide other benefits, or at least provide the public with a useful choice. (
  • CD137's signaling domain is included in approved chimeric antigen receptors conferring persistence and efficacy. (
  • In chimeric antigen receptor (CAR) T-cell immunotherapy, autologous effector T-cells are harvested from the peripheral blood of patients with cancer through leukapheresis and genetically engineered ex vivo using a lentiviral or gammaretroviral vector to express synthetic proteins known as CAR receptors. (
  • 1-4 These receptors are directed against pre-determined cell-surface antigens expressed on tumor cells. (
  • Persistence of T cells engineered with chimeric antigen receptors (CARs) has been a major barrier to use of these cells for molecularly targeted adoptive immuno-therapy. (
  • En tredje Co-domän ingår för att förbättra T-cells funktion, engrafktion, Chimeric receptors containing CD137 signal transduction domains Fältet av chimära antigen receptorn (bil) T-cellterapi går snabbt framåt med Denna analys kan kopplas till profilering T cellaktivering, utmattning och minne fenotyper. (
  • T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca 2+ ) concentration. (
  • Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca 2+ signaling and promote T cell survival. (
  • Co-receptors play a fundamental role in regulating and fine-tuning the signal strength of so-called antigen receptors, which help immune cells to recognize foreign bodies. (
  • A subclass of NK cell lectin-like receptors that associates with a variety of members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY C to form heterodimeric receptors for HLA-E antigen. (
  • Chimeric antigen receptor (CAR) T-cell remedy is an progressive type of immunotherapy whereby autologous T-cells are genetically modified to specific chimeric receptors encoding an antigen-specific single-chain variable fragment and costimulatory molecules. (
  • In adoptive CD8+ T-cell remedy (ACT), quite a few tumor-specific, engineered T-cells are sourced from sufferers, expanded in vitro , and infused again expressing tumor-specific antigen receptors. (
  • Chimeric antigen receptors ( CARs , also known as chimeric immunoreceptors , chimeric T cell receptors or artificial T cell receptors ) are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen . (
  • The receptors are chimeric because they combine both antigen-binding and T cell activating functions into a single receptor. (
  • In brief, CAR-T takes immune cells called T cells from a patient, genetically engineers them to express chimeric antigen receptors (CARs) that recognize the patient's cancer cells, and re-infuses them back to the patient (this process is called adoptive cell transfer, or ACT). (
  • The development of chimeric antigen receptors (CARs) provided a more universal approach to cancer immunotherapy since CARs can recognize cell surface antigens in an MHC-independent manner. (
  • first characterized the phenotype of tumor-specific CD8 + TCRs followed by the use of gBlocks™ Gene Fragments for TCR reconstruction and antigen specificity to develop reactivity studies which allowed them to determine the specificity and avidity of true anti-melanoma lymphocytes that had more targeted immune response to those cancer cells [2]. (
  • In addition, TCR reconstruction and antigen specificity screening was done and a CD137 upregulation assay was run to determine the TCR transduction signal stemming from antigen recognition [2]. (
  • Conclusion Tandem CARs are equally effective in standard disease models to single antigen specificity CARs, and may be both more effective and less toxic in a higher disease burden setting. (
  • Many studies have shown that compared the 1st generation, the 2nd generation of CAR with the "second signal" remains the same level of antigen specificity with the increment of T cell proliferation, cytokine secretion, anti-apoptotic protein secretion and the delay of cell death. (
  • During preclinical research and development, CAR (chimeric antigen receptor) T-cell therapies are often investigated using a mouse as the test subject. (
  • Essentially the most profitable ACT, anti-CD19 chimeric antigen receptor T-cell remedy directed in opposition to B-cell lymphoma, has proved to be efficacious. (
  • Similar in presentation to a "cytokine storm", which can be observed across a variety of diseases and treatments, CRS has recently become more formally associated with T-cell-engaging immunotherapies, such as blinatumomab and chimeric antigen receptor T-cell (CAR-T) therapy . (
  • Moreover, IL-21's antitumor activity can be potentiated by its combination with other immune-enhancing molecules, monoclonal antibodies recognizing tumor antigens, chemotherapy, or molecular targeted agents. (
  • Many WAY-262611 of these molecules are the targets of therapeutic agents Rabbit polyclonal to HOMER1 that are FDA approved (ipilimumab for CTLA-4)or are in clinical (PD-1, CD137 or 4-1BB) (12, 13)or pre-clinical (Tim-3)(14, 15) trials. (
  • The company designs molecules with two natural binding sites and two additional antigen binding sites in the Fc region. (
  • It first transforms a fragment of scFv, an antibody capable of recognizing a specific tumor antigen and then integrates the fragment into the transmembrane chain segment composed of different combinations of molecules such as CD3-ζ, CD137, NKG2D and DAP10, forming a forming a recombinant plasmid CAR. (
  • Assessment expression of the molecules CD134 and CD137 in patients with colorectal cancer. (
  • Foreign antigen fragments presented by specific major histocompatibility complex (in humans, called human leukocyte antigens or HLAs) molecules are essentially ligands for the TCR. (
  • 5-7 The extracellular antigen-binding domain is derived from a single-chain variable fragment (scFv) constructed through fusion of the antigen-binding regions of both heavy (VH) and light (VL) chains of a monoclonal antibody. (
  • Polyclonal antibody for CD137/TNFRSF9 detection. (
  • Agonistic anti-CD137 antibody acts as an activating costimulatory molecule especially important for effector/memory T cells and promotes the sur 2017-06-24 · CD137 can maintain the response signal of T cells, which plays a key role in the survival of T cells and the memory of CD8 + T cells [19,20,21]. (
  • The CAR is a fusion antigen receptor: part antibody, part TCR, made up of an extracellular antigen-binding, transmembrane and intracellular signaling domain(s). (
  • To address this issue, we created a series of CARs that contain the T cell receptor-ζ (TCR-ζ) signal transduction domain with the CD28 and/or CD137 Se hela listan på 2019-04-22 · 61 insight into how CD137 costimulation of effector T cells, independent of plaque-antigen 62 recognition, instigates their retention and promotes innate-like responses from immune 63 infiltrates within atherogenic foci. (
  • OverviewProduct Name:Mouse 4-1BBR Recombinant ProteinProduct Code:RPPB5744Size:5µgSpecies:MouseTarget:4-1BBRSynonyms:Tumor necrosis factor receptor superfamily member 9, 4-1BB ligand receptor, T-cell antigen 4-1BB, CD137.Source:Sf9 Insect. (
  • Here, we developed and validated a simple and time efficient method for the selection of T cells expressing CD28 and CD137 domain-containing CARs pro-duced greater quantities of IL-2 when compared with cells express-ing the αCD19-ζ receptor (Figure 3). (
  • CD28 and CD137(4-1BB) are two alternative CARs for different tumors in vivo and vitro. (
  • In assessing the accuracy and avidity of the antitumor TCRs, they found that this exhaustive phenotype continued to be observed whether it was a public melanoma antigen (MAA) distributed among different tumors, or a personal neoantigen (NeoAg) specific for each tumor [2]. (
  • Twenty-five years ago, we reported that agonist anti-CD137 monoclonal antibodies eradicated transplanted mouse tumors because of enhanced CD8+ T-cell antitumor immunity. (
  • A new wave of CD137 agonists targeting tumors, mainly based on bispecific constructs, are in early-phase trials and are showing promising safety and clinical activity. (
  • The necessary and persistent (7)expression of MCPyV T-antigen (T-Ag) oncoproteins in MCC tumors provides an opportunity to study anti-tumor immunity by assessing responses against a viral, tumor-specific antigen. (
  • Once isolated from a person, these T cells are genetically engineered to express a specific CAR, which programs them to target an antigen that is present on the surface of tumors. (
  • [15] Similar early clinical trials of CAR T cells in solid tumors in the 1990s using first generation CARs targeting a solid tumor antigens such as MUC1 did not show long-term persistence of the transferred T cells or result in significant remissions. (
  • Here, we evaluated the immunobiology of CD137 in human cancer and the utility of a CD137-positive separation methodology for the identification and enrichment of fresh tumor-reactive tumor-infiltrating lymphocytes (TIL) or tumor-associated lymphocytes (TAL) from ascites for use in adoptive immunotherapy. (
  • In this study we investigated the use of a novel chimeric antigen receptor (CAR) targeting the disialoganglioside GD2 for sarcoma immunotherapy. (
  • Background Clinical success with chimeric antigen receptor (CAR)- based immunotherapy for leukemia has been accompanied by the associated finding that antigen-escape variants of the disease are responsible for relapse. (
  • SIGNIFICANCE: CD137 (4-1BB) is a costimulatory receptor of T and natural killer lymphocytes whose activity can be exploited in cancer immunotherapy strategies as discovered 25 years ago. (
  • Recent studies have also investigated CD137 as an attractive target for cancer immunotherapy. (
  • Chimeric antigen receptor T cells (also known as CAR T cells ) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy . (
  • The ability of T cells to recognize and eradicate cancer cells expressing foreign tumor-associated antigens (TAAs) has been an area of interest for cancer immunotherapy for the past few decades. (
  • CD137 is a type I membrane protein and a member of the tumor necrosis factor receptor superfamily. (
  • The rapid co-modulation of CD19, CD20, and CD22 may account for the ability to rapidly evolve escape mutants by selecting for leukemic clones that not require these target antigens for continued expansion. (
  • Currently, CAR T-cell therapy is being investigated for the treatment of relapsed or refractory multiple myeloma (MM). 14,19-22 The principal target of CAR T-cell therapies for multiple myeloma is the B-cell maturation antigen (BCMA). (
  • CusabioAlternative Name(s): B-cell maturation protein (CD_antigen: CD269) (Bcm). (
  • A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. (
  • Upregulation of CD137 (4-1BB) on recently activated CD8 + T cells has been used to identify rare viral or tumor antigen-specific T cells from peripheral blood. (
  • Immune checkpoint proteins can regulate the immune response in malignancies and infectious diseases via numerous types of activating and inhibitory signals between antigen-presenting cells (APCs) and T cells [ 3 , 4 ]. (
  • TCR CAR-T cells against various tumor antigens have been developed (Ma et al. (
  • Tandem-CARs were compared to single antigen targeting CARs in vitro and in vivo, and to an admixture of transduced cells expressing each CAR in vivo in immunodeficient (NSG) disease-bearing mice. (
  • We also demonstrated that tumor-induced impairment of the antigen-presenting function of GAMs could limit the antitumor immunity of CD4+ T cells in anti-PD-1 therapy. (
  • Preclinical studies have demonstrated that BT7480 activates CD137 only in the presence of Nectin-4 expressing tumor cells. (
  • What Are Chimeric Antigen Receptor (CAR) T-cells and What is Their Potential Target Site in Multiple Myeloma? (
  • 1-4 Lymphodepleting chemotherapy is given to the patient and then the re-programmed CAR T-cells are infused back into the patient, where they induce a selective immune response against tumor cells expressing the corresponding antigen. (
  • Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. (
  • CD137 engagement by CD137L on antigen-activated T cells increases proliferation, effector functions, and survival, in both mouse and human. (
  • CD137 + T-cells are largely known to be the anti-tumor activated effector cells, but they have never been associated with the response to immunotherapies. (
  • CD137 is involved in the activation of T cells, NK cells, B cells and APV-527 selektivt aktiverar och förstärker T-cellers och NK-cellers tumörriktade. (
  • receptorn 4-1BB (CD137) på aktiverade cytotoxiska T-celler och NK (Natural Den uppvisar egenskaper såsom målstyrd T-cells-aktivering, 4-1BB (CD137) för att främja potent, tumörriktad T-cellsaktivering. (
  • CD137 is expressed by activated T cells, dendritic cells, NK cells, granulocytes av A Karlsson-Parra - ligand as additional intratumoral immune priming approach. (
  • We further compared the phenotype and function of CD137 + and CD137 CD137 (4-1BB) has been identified as a co-stimulatory marker, which is induced upon the specific interaction of T cells with their target cell. (
  • Therefore, CD137 can be a useful biomarker and an important tool for the selection of tumor-reactive T cells. (
  • The ability of ilixadencel to up-regulate CD137-expression on co-cultured allogeneic NK cells and T av G Fotaki · 2019 - (alloDCs), not for direct antigen-presentation to T cells but as an immune primer targeting of PD-1 or CD137 enhances the effect of adjuvant. (
  • anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. (
  • Workflows have been developed for the expansion of pathogen-specific CD4 or CD8 T cells expressing CD137, which can then be used in screens against pathogen protein libraries to identify those that specifically activate T cells (e.g. proliferation or cytokine secretion). (
  • Expanded T cells are screened in stimulations with pathogen proteins in the presence of autologous PBMC as antigen-presenting cells (APC). (
  • Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. (
  • After several stimulations, the CD8 T cells become evaluated on their cytokine secretion, cytotoxicity and % of antigen specific T cells. (
  • We previously described mRNA electroporation as an efficient gene delivery method to introduce tumor-antigens (Ag) into murine immature dendritic cells (DC). (
  • CD137 or 4-1BB is a co-stimulatory molecule which is frequently expressed on activated T cells to ensure a proper T cell function. (
  • The adoptively transferred cells are directed by the engineered chimeric antigen receptor to bind to a surface antigen on a tumor cell (CD19 for example). (
  • Adoptive mobile approaches using chimeric antigen receptor T cells (CAR-T) concentrating on cancer-specific antigens could be an answer for circumventing the immune tolerance mechanisms. (
  • For safety, CAR T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells. (
  • [4] When they come in contact with their targeted antigen on a cell, CAR T cells bind to it and become activated, then proceed to proliferate and become cytotoxic . (
  • A first generation CAR containing a CD4 extracellular domain and a CD3ζ intracellular domain was used in the first clinical trial of chimeric antigen receptor T cells by the biotechnology company Cell Genesys in the mid 1990s, allowing adoptively transferred T cells to target HIV infected cells, although it failed to show any clinical improvement. (
  • These engineered cells circulate in the bloodstream, becoming "living drugs" that target and kill the antigen-expressing cancer cells. (
  • TCRs engineered to recognize MART-1 antigen, which is highly expressed on malignant melanoma cells, resulted in T cells with high avidity for malignant cells. (
  • When the CAR binds to a tumor antigen on the surface of a target cell, the CAR T cell will induce apoptosis using the same mechanism as normal T cells. (
  • The transmembrane domain connects the scFv, which specifies the T cell binding to a tumor antigen to the intracellular CD3ζ domain, responsible for T cell activation. (
  • CD137 is a 39 kD transmembrane protein also known as 4-1BB. (
  • Methods Antigen binding domains from the FMC63 (anti-CD19) and Leu16 (anti-CD20) antibodies were linked in differing configurations to transmembrane and T cell signaling domains to create tandem-CARs. (
  • A read-out assay such as 3 H-thymidine incorporation or cytokine secretion is used to identify the targets of antigen-specific responses. (
  • Co-stimulatory receptor-ligand interactions that help amplify effector T cell responses include CD28-CD80, 4-1BB (also known as CD137)-4-1BB ligand, CD27-CD70. (
  • 4-1BBL (CD137L) and 4-1BB (CD137) are a receptor ligand pair belonging to the tumor necrosis factor (TNF) receptor/TNF superfamily 1,2 . (
  • CD137 is closely related to CD27, OX40, and CD30. (
  • Following initial attempts that met unacceptable toxicity, new waves of constructs acting agonistically on CD137 are being developed in patients, offering signs of clinical and pharmacodynamic activity with tolerable safety profiles. (
  • All four patients had a germline mutation in the gene encoding CD137, which led to a dysfunction of the co-receptor protein CD137. (
  • Home » CD137+CD154- Expression As a Regulatory T Cell (Treg)-Specific Activation Signature for Identification and Sorting of Stable Human Tregs from In Vitro Expansion Cultures. (
  • and BT7480, a Bicycle TICA™ targeting Nectin-4 and stressful CD137, in company-sponsored Phase I/II trials. (
  • and BT7480, a Bicycle TICA™ targeting Nectin-4 and agonizing CD137, in company-sponsored Phase I/II trials. (
  • Mouse models indicated that anti-CD137 agonist antibodies synergized with various other therapies. (
  • Right here, we current a abstract of state-of-the-art R-based pipelines used for differential analyses of cytometry information, largely primarily based on chimeric antigen receptor (CAR) T cell therapies. (
  • On the other hand, NeoAg-specific TCRs had a much higher binding strength due to high affinity and increased stability from mutated peptide-HLA interactions resulting from a much lower expression of its associated antigen [2]. (
  • While it is possible to engineer TCRs to recognize many different tumor antigens, the mechanism of T cell activation is a limiting factor for their use for ACT. (
  • Activation of CD137, a co-stimulatory receptor expressed on multiple components of the immune system, can drive anti-tumor immunity, but activation outside of the tumor may give rise to toxicity. (
  • Not only did we discover a new tumor predisposition syndrome particularly for childhood lymphomas in this study, we also learned more about the basic function of CD137 in the immune system. (
  • Thus, we can gain mechanistic insights into the signal pathways necessary for a robust immune surveillance of the host against EBV.In summary, this study demonstrates the key role of CD137 in the control of EBV virus by the immune system. (
  • Activation-induced cell death (AICD) is a complex immunoregulatory mechanism that causes the demise of a fraction of T-lymphocytes upon antigen-driven activation. (
  • PHA-stimulated (three days) human peripheral blood lymphocytes were stained with CD137 (clone 4B4-1) Brilliant Violet 605™ (filled histogram) or mouse IgG1, κ Brilliant Violet 605™ (open histogram). (
  • CD8 + tumor-specific tumor infiltrating lymphocytes (TILs) predominantly result in an exhausted phenotype when interacting with tumor antigens [2]. (
  • 5. Ramos CA, Dotti G. Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy. (
  • Immunohistochemical staining is positive for hepatitis B surface antigen (HBsAg. (
  • [ 2 ] In addition, immunoglobulin and vaccination should be administered to newborns born to women positive for hepatitis B surface antigen (HBsAg). (
  • CD137 appears to be important for T cell proliferation and survival, and induces monocyte activation through its interaction with 4-1BB ligand. (
  • 64 65 Keywords: Atherosclerosis, Inflammation, CD137, CD8 T cell, IFNγ 66 67 NEW & NOTEWORTHY T cell responses in anti-CD137-injected mice +was evident in the spleen, LN, lung, and liver of treated mice (Figure 2 and data not shown). (
  • To target hematologic malignancies with a chimeric antigen receptor (CAR) that targets two antigens with a single vector, and thus potentially lessen the chance of leukemic escape mutations, a tandem-CAR approach was investigated. (