Antigens: Substances that are recognized by the immune system and induce an immune reaction.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Antigens, Neoplasm: 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.Receptors, Antigen, T-Cell: 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.Antigens, Surface: 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.Lymphoma, T-Cell: A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Molecular Sequence Data: 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.T-Lymphocytes: 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.Antigens, CD3: 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).Amino Acid Sequence: 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.Gene Fusion: The GENETIC RECOMBINATION of the parts of two or more GENES resulting in a gene with different or additional regulatory regions, or a new chimeric gene product. ONCOGENE FUSION includes an ONCOGENE as at least one of the fusion partners and such gene fusions are often detected in neoplastic cells and are transcribed into ONCOGENE FUSION PROTEINS. ARTIFICIAL GENE FUSION is carried out in vitro by RECOMBINANT DNA technology.Receptors, Antigen, T-Cell, alpha-beta: 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.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Antigens, CD: 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.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Sodium-Potassium-Exchanging ATPase: An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients.HLA Antigens: 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.Lymphocyte Activation: 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.Antigens, Polyomavirus Transforming: 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.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Leukemia, T-Cell: A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.Leukemia-Lymphoma, Adult T-Cell: Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.Lymphoma, T-Cell, Cutaneous: A group of lymphomas exhibiting clonal expansion of malignant T-lymphocytes arrested at varying stages of differentiation as well as malignant infiltration of the skin. MYCOSIS FUNGOIDES; SEZARY SYNDROME; LYMPHOMATOID PAPULOSIS; and PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA are the best characterized of these disorders.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, Fungal: Substances of fungal origin that have antigenic activity.H-2 Antigens: The major group of transplantation antigens in the mouse.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Lymphoma, T-Cell, Peripheral: A group of malignant lymphomas thought to derive from peripheral T-lymphocytes in lymph nodes and other nonlymphoid sites. They include a broad spectrum of lymphocyte morphology, but in all instances express T-cell markers admixed with epithelioid histiocytes, plasma cells, and eosinophils. Although markedly similar to large-cell immunoblastic lymphoma (LYMPHOMA, LARGE-CELL, IMMUNOBLASTIC), this group's unique features warrant separate treatment.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Epitopes: Sites on an antigen that interact with specific antibodies.CD4-Positive T-Lymphocytes: 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.Carcinoembryonic Antigen: 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.Histocompatibility Antigens: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Antigens, Viral, Tumor: 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.Histocompatibility Antigens Class II: 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.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Antigens, CD8: 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.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Receptors, Antigen, T-Cell, gamma-delta: T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).Recombinant Fusion Proteins: 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.Mice, Inbred BALB CElectrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.HLA-A2 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.HLA-DR Antigens: 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.Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.Receptors, Antigen, B-Cell: 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.Proliferating Cell Nuclear Antigen: 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.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Kinetics: The rate dynamics in chemical or physical systems.Mice, Inbred C57BLEnzyme-Linked Immunosorbent Assay: 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.Prostate-Specific Antigen: 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.Antigens, CD4: 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.Flow Cytometry: 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.O Antigens: 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)B-Lymphocytes: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.HLA-A Antigens: 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.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Antigens, CD45: 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.Antigens, CD15: 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.Histocompatibility Antigens Class I: 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.Interferon-gamma: 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.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Antigens, Tumor-Associated, Carbohydrate: 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.T-Lymphocytes, Cytotoxic: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Cells, Cultured: 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.Clone Cells: 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)Immunization: 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).Hepatitis B Surface Antigens: 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.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Dendritic Cells: 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).Antibody Specificity: 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.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Blood Group Antigens: Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.HLA-D Antigens: 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.Antigen-Presenting Cells: 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.Immunity, Cellular: 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.Antigens, Differentiation: 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.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.Antigens, CD80: 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.Fluorescent Antibody Technique: 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.Antigens, CD1: 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.Thymus Gland: 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.Cytotoxicity, Immunologic: 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.HLA-B 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.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.MART-1 Antigen: 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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Immune Tolerance: 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.Hepatitis B Antigens: 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.Immune Sera: 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.Mice, Inbred Strains: 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.HIV Antigens: 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.Immunophenotyping: 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.Immunologic Memory: 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.Human T-lymphotropic virus 1: A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).Immunoenzyme Techniques: 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.T-Cell Antigen Receptor Specificity: The property of the T-CELL RECEPTOR which enables it to react with some antigens and not others. The specificity is derived from the structure of the receptor's variable region which has the ability to recognize certain antigens in conjunction with the MAJOR HISTOCOMPATIBILITY COMPLEX molecule.Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Antigens, CD28: 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.Cytokines: 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.Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.Lymphocytes: 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.Antibodies: 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).Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Major Histocompatibility Complex: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Antigens, CD40: 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.CTLA-4 Antigen: 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.Antigens, CD2: 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.Epstein-Barr Virus Nuclear Antigens: Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.Antigens, CD86: 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.Peptides: 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.Hybridomas: 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.Antigens, Thy-1: 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.Leukemia, Prolymphocytic, T-Cell: A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.T-Lymphocytes, Helper-Inducer: Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.Antigens, Heterophile: Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.Immunoglobulin M: 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.Cancer Vaccines: Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Hepatitis B Core Antigens: The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.H-Y Antigen: 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.HLA-DQ Antigens: 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.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.Receptor, Interferon alpha-beta: A ubiquitously expressed heterodimeric receptor that is specific for both INTERFERON-ALPHA and INTERFERON-BETA. It is composed of two subunits referred to as IFNAR1 and IFNAR2. The IFNAR2 subunit is believed to serve as the ligand-binding chain; however both chains are required for signal transduction. The interferon alpha-beta receptor signals through the action of JANUS KINASES such as the TYK2 KINASE.Molecular Weight: The sum of the weight of all the atoms in a molecule.Antigen-Antibody Complex: 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.Receptor-CD3 Complex, Antigen, T-Cell: Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Tumor Cells, Cultured: 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.Genes, T-Cell Receptor beta: DNA sequences encoding the beta chain of the T-cell receptor. The genomic organization of the TcR beta genes is essentially the same in all species and is similar to the organization of Ig genes.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.gp100 Melanoma Antigen: A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.Isoantigens: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.T-Lymphocytes, Regulatory: 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.Antigens, CD95: 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, CD7: 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.Rabbits: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Vaccines, Synthetic: Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Forssman Antigen: 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.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Genes, T-Cell Receptor: DNA sequences, in cells of the T-lymphocyte lineage, that code for T-cell receptors. The TcR genes are formed by somatic rearrangement (see GENE REARRANGEMENT, T-LYMPHOCYTE and its children) of germline gene segments, and resemble Ig genes in their mechanisms of diversity generation and expression.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Gene Products, tax: Transcriptional trans-acting proteins of the promoter elements found in the long terminal repeats (LTR) of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The tax (trans-activator x; x is undefined) proteins act by binding to enhancer elements in the LTR.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Herpesvirus 4, Human: 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.Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen.Signal Transduction: 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.Complement Fixation Tests: 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.RNA, Messenger: 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.Mice, Inbred CBAImmunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Immunotherapy, Adoptive: Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)Adjuvants, Immunologic: 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, CD30: 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.Antigens, CD27: A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antigens, CD79: 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.Transfection: 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.Antigens, CD58: 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.Antigens, Differentiation, T-Lymphocyte: 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.Mice, Inbred C3HSensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Antigens, T-Independent: Antigens which may directly stimulate B lymphocytes without the cooperation of T lymphocytes.Immunoelectrophoresis: 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.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Vaccines, DNA: Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Antigens, CD5: 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)HLA-A1 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*01 allele family.

*  Genetically engineered T cells for the treatment of cancer.

However, it has been limited by the ability to isolate and expand T cells restricted to tumour-associated antigens. Using ex ... vivo gene transfer, T cells from patients can be g ... T-cell immunotherapy is a promising approach to treat ... The TCR is a heterodimer formed by the pairing of an alpha chain and a beta chain. The receptor interacts with an antigenic ... T cells can be genetically engineered to express a unique high-affinity T cell receptor (TCR) or a chimeric antigen receptor ( ...

*  Filaggrin deficient mice exhibit Th17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein...

An obligate role for T-cell receptor alpha beta T+ cells but not T-cell receptor gamma delta T+ cells, B cells, or CD40/CD40L ... Antigen entry via a disrupted skin barrier in ft/ft mice may lead to development of eczematous skin lesions with age. Fig. 1A ... Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature. 2008;453:1051-7. [PubMed] ... T cells and Gr-1+ neutrophils, but not CD11c+ dendritic cells, compared to ear skin from controls (Fig. 2C). There was no ...

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T-Cell Receptor Alpha Variable 19, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - ... In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. If both ... molecules at the surface of antigen presenting cells (APC). Each T cell receptor is a dimer consisting of one alpha and one ... the cell proceeds to rearrange the beta and alpha loci. This region represents the germline organization of the T cell receptor ...

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T cell receptor *A transmembrane receptor made of alpha and beta subunits, both of which contain a variable and a constant ... Non-classical: Polymorphic; are used to present antigen to αβ T cells, γδ T cells, NK cells and NK T cells*Class I: Binds short ... Primed T cells immediately increase the IL-2 receptor affinity by upregulating the alpha subunit; the primed T cell can then ... A cell surface receptor that signals a common lymphoid progenitor cell to differentiate into a T cell lineage and not a B cell ...

*  2015 Strategies in the UK Tumor Marker Testing Market - market research report

Prostate-Specific Antigen (PSA). 21. Squamous Cell Carcinoma Antigen (SCC). 22. T and B Lymphocytes. 23. TdT. 24. Thyroglobulin ... 4. Alpha-Fetoprotein (AFP). 5. Beta-2 Microglobulin. 6. CA 15-3/27.29. 7. CA 19-9. 8. CA-125. 9. Calcitonin. 10. ... Carcinoembrionic Antigen (CEA). 11. Estrogen and Progesterone Receptors. 12. Ferritin. 13. Gastrin. 14. Human Chorionic ... Alpha-Interferon. - B Cell Growth Factors. - B Cell Growth Factor (BCGF). - Gamma-Interferon. - Interleukin-1 (IL-1). - ...

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Prostate-Specific Antigen (PSA). 21. Squamous Cell Carcinoma Antigen (SCC). 22. T and B Lymphocytes. 23. TdT. 24. Thyroglobulin ... 4. Alpha-Fetoprotein (AFP). 5. Beta-2 Microglobulin. 6. CA 15-3/27.29. 7. CA 19-9. 8. CA-125. 9. Calcitonin. 10. ... Carcinoembrionic Antigen (CEA). 11. Estrogen and Progesterone Receptors. 12. Ferritin. 13. Gastrin. 14. Human Chorionic ... Peripheral T-cell Lymphoma - Competitive L ... July 2017 $ 6950 Cutaneous Squamous Cell Carcinoma- Competi ... July 2017 $ 6950 ...

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Point mutation of Gln136 affects antigen responsiveness. Hybridomas expressing the wt TCR-α chain and wt or mutant β chains ... Receptors, Antigen, T-Cell, alpha-beta/chemistry/genetics*/immunology*. *Receptors, Antigen, T-Cell, gamma-delta/chemistry/ ... Receptors, Antigen, T-Cell, alpha-beta/chemistry/genetics*/immunology*. *Receptors, Antigen, T-Cell, gamma-delta/chemistry/ ... Signaling efficiency of the T cell receptor controlled by a single amino acid in the beta chain constant region. ...

*  IL-27: Balancing T Cell-Mediated Immune Responses: R&D Systems

Each of these cytokines consists of an alpha (p19, p28, or p35) and a beta (p40 or EBI3) chain and signals through receptors ... 2 Upon secretion by activated antigen-presenting cells, IL-27 promotes the expansion of naïve CD4+ T cells, and drives Th1 ... T cells.13 This was accompanied by reduced expression of GATA-3 and RORC. Addition of IL-2 to activated T cells significantly ... IL-27-treated T cells suppressed the proliferation of freshly purified CD4+ T cells in an IL-10-dependent manner.13 ...

*  Comparison of Humoral and Cell Mediated Immunity - howMed

Receptors. B-cell antigen receptor complex consisting of mainly IgM and IgD immunoglobulins. In 95% T cells à alpha/beta TCR ... Antigen receptor recognizes whole unprocessed proteins and has no requirement for presentation by MHC protein. Antigen receptor ... Differentiation of B cells into antibody secreting cells called plasma cells. Secrete locally acting proteins called cytokines ... Main cells. B lymphocytes. T lymphocytes. Maturation. Generated and matured in bone marrow. Originate in bone marrow and ...

*  Pathogenic CD8 T Cells in Multiple Sclerosis and Its Experimental Models

Reconstitution of paired T cell receptor alpha- and beta-chains from microdissected single cells of human inflammatory tissues ... Davis M. M., Bjorkman P. J. (1988). T-cell antigen receptor genes and T-cell recognition. Nature 334, 395-40210.1038/334395a0 [ ... Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell ... Cellular Targets of Pathogenic CD8 T Cells. *Why are Pathogenic CNS-Reactive CD8 T Cells Present within the Mature T Cell ...

History and naming of human leukocyte antigens: Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types.Cancer/testis antigen family 45, member a5Kinetic-segregation model of T cell activationColes PhillipsPMHC cellular microarray: PMHC cellular microarrays are a type of cellular microarray that has been spotted with pMHC complexes peptide-MHC class I or peptide-MHC class II.VisilizumabProtein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.CD36 antigen: CD36 antigen is a transmembrane, highly glycosylated, glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. CD36 recognises oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin and Plasmodium falciparum infected erythrocytes.FXYD familyHLA B7-DR15-DQ6Database of protein conformational diversity: The Database of protein conformational diversity (PCDB) is a database of diversity of protein tertiary structures within protein domains as determined by X-ray crystallography. Proteins are inherently flexible and this database collects information on this subject for use in molecular research.Adult T-cell leukemia/lymphomaCutaneous lymphoma: There are two classes of lymphomas that affect the skin:Symmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Reaction coordinateChemically induced dimerization: Chemically Induced Dimerization (CID) is a biological mechanism in which two proteins bind only in the presence of a certain small molecule, enzyme or other dimerizing agent. Genetically engineered CID systems are used in biological research to control protein localization, to manipulate signalling pathways and to induce protein activation.Monoclonal antibody therapyPeripheral T-cell lymphomaTransmembrane domain: Transmembrane segment usually denotes a single transmembrane alpha helix of a transmembrane protein, also known as an integral protein.http://www.Cryptic self epitopes: In immunology, cryptic self epitopes are a source of autoimmunity.Carcinoembryonic antigen: Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth.MHC class IIThermal cyclerCD79: CD79 (Cluster of Differentiation 79) is a transmembrane protein that forms a complex with the B-cell receptor (BCR) and generates a signal following recognition of antigen by the BCR. CD79 is composed of two distinct chains called CD79A and CD79B (formerly known as Ig-alpha and Ig-beta); these form a heterodimer on the surface of a B cell stabilized by disulfide bonding.Proximity ligation assay: Proximity ligation assay (in situ PLA) is a technology that extends the capabilities of traditional immunoassays to include direct detection of proteins, protein interactions and modifications with high specificity and sensitivity. Protein targets can be readily detected and localized with single molecule resolution and objectively quantified in unmodified cells and tissues.Margaret Jope: Margaret Jope (1913–2004) was a Scottish biochemist, born as Henrietta Margaret Halliday in Peterhead, Scotland.DNA binding site: DNA binding sites are a type of binding site found in DNA where other molecules may bind. DNA binding sites are distinct from other binding sites in that (1) they are part of a DNA sequence (e.Tubulin: Tubulin ([+ -in]) in [[molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton.FERM domain: In molecular biology, the FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane.Burst kinetics: Burst kinetics is a form of enzyme kinetics that refers to an initial high velocity of enzymatic turnover when adding enzyme to substrate. This initial period of high velocity product formation is referred to as the "Burst Phase".Eva Engvall: Eva Engvall, born 1940, is one of the scientists who invented ELISA in 1971.Eva Engvall, The Scientist 1995, 9(18):8KeliximabFlow cytometry: In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.PerosaminePolyclonal B cell response: Polyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of B cell.HLA-A: HLA-A is a group of human leukocyte antigens (HLA) that are coded for by the HLA-A locus, which is located at human chromosome 6p21.3.CD4 immunoadhesin: CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region.Antigen presentation: Antigen presentation describes a vital process of the immune system. Immune cells cannot "see inside" other cells, which may be infected with viruses or bacteria, and thus rely on information conveyed by fragments of intracellular components being presented on major histocompatibility complex (MHC) molecules on the cell surface.List of strains of Escherichia coli: Escherichia coli is a well studied bacterium that was first identified by Theodor Escherich, after whom it was later named.CTL-mediated cytotoxicityPeriarteriolar lymphoid sheaths: Periarteriolar lymphoid sheaths (or periarterial lymphatic sheaths, or PALS) are a portion of the white pulp of the spleen. They are populated largely by T cells and surround central arteries within the spleen; the PALS T-cells are presented with blood borne antigens via myeloid dendritic cells.Knotted protein: Knotted proteins are proteins whose backbones entangle themselves in a knot. One can imagine pulling a protein chain from both termini, as though pulling a string from both ends.ImmunizationExbivirumabAcute myeloid dendritic cell leukemia: Acute myeloid dendritic cell leukemia is an exceedingly rare form of leukemia. This form of leukemia represents only about 0.Indian blood group system: The Indian blood group system (In) is a classification of blood based on the presence or absence of inherited antigens that reside within the CD44 molecule that is expressed on the surface of blood cells. It is named so because 4% of the population in India possess it.HLA-DMCell-mediated immunity: Cell mediated immunity is an immune response that does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells.Hassall's corpuscles: Hassall's corpuscles (or thymic corpuscles (bodies)) are structures found in the medulla of the human thymus, formed from eosinophilic type VI epithelial reticular cells arranged concentrically. These concentric corpuscles are composed of a central mass, consisting of one or more granular cells, and of a capsule formed of epithelioid cells.Escheriosome: Escheriosomes are liposomes prepared from polar lipids extracted from Escherichia coli. Such kinds of delivery vehicles have been shown to elicit high cytotoxic T lymphocyte (CTL) responses.

(1/3508) A new element within the T-cell receptor alpha locus required for tissue-specific locus control region activity.

Locus control regions (LCRs) are cis-acting regulatory elements thought to provide a tissue-specific open chromatin domain for genes to which they are linked. The gene for T-cell receptor alpha chain (TCRalpha) is exclusively expressed in T cells, and the chromatin at its locus displays differentially open configurations in expressing and nonexpressing tissues. Mouse TCRalpha exists in a complex locus containing three differentially regulated genes. We previously described an LCR in this locus that confers T-lineage-specific expression upon linked transgenes. The 3' portion of this LCR contains an unrestricted chromatin opening activity while the 5' portion contains elements restricting this activity to T cells. This tissue-specificity region contains four known DNase I hypersensitive sites, two located near transcriptional silencers, one at the TCRalpha enhancer, and another located 3' of the enhancer in a 1-kb region of unknown function. Analysis of this region using transgenic mice reveals that the silencer regions contribute negligibly to LCR activity. While the enhancer is required for complete LCR function, its removal has surprisingly little effect on chromatin structure or expression outside the thymus. Rather, the region 3' of the enhancer appears responsible for the tissue-differential chromatin configurations observed at the TCRalpha locus. This region, herein termed the "HS1' element," also increases lymphoid transgene expression while suppressing ectopic transgene activity. Thus, this previously undescribed element is an integral part of the TCRalphaLCR, which influences tissue-specific chromatin structure and gene expression.  (+info)

(2/3508) Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL.

T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2Kb-restricted glycopeptide RGY8-6H-Gal2 generates a population of cytotoxic T cells that express both alpha/beta TCR, specific for glycopeptide, and gamma/delta TCR, specific for the disaccharide, even on glycolipids. The crystal structure of Kb/RGY8-6H-Gal2 now demonstrates that the peptide and H-2Kb structures are unaffected by the peptide glycosylation, but the central region of the putative TCR binding site is dominated by the extensive exposure of the tethered carbohydrate. These features of the Kb/RGY8-6H-Gal2 structure are consistent with the individual ligand binding preferences identified for the alpha/beta and gamma/delta TCRs and thus explain the generation of a carbohydrate-specific T cell response.  (+info)

(3/3508) The stability and fate of a spliced intron from vertebrate cells.

Introns constitute most of the length of typical pre-mRNAs in vertebrate cells. Thus, the turnover rate of introns may significantly influence the availability of ribonucleotides and splicing factors for further rounds of transcription and RNA splicing, respectively. Given the importance of intron turnover, it is surprising that there have been no reports on the half-life of introns from higher eukaryotic cells. Here, we determined the stability of IVS1Cbeta1, the first intron from the constant region of the mouse T-cell receptor-beta, (TCR-beta) gene. Using a tetracycline (tet)-regulated promoter, we demonstrate that spliced IVS1Cbeta1 and its pre-mRNA had half-lives of 6.0+/-1.4 min and 3.7+/-1.0 min, respectively. We also examined the half-lives of these transcripts by using actinomycin D (Act.D). Act.D significantly stabilized IVS1Cbeta1 and its pre-mRNA, suggesting that Act.D not only blocks transcription but exerts rapid and direct posttranscriptional effects in the nucleus. We observed that in vivo spliced IVS1Cbeta1 accumulated predominantly as lariat molecules that use a consensus branchpoint nucleotide. The accumulation of IVS1Cbeta1 as a lariat did not result from an intrinsic inability to be debranched, as it could be debranched in vitro, albeit somewhat less efficiently than an adenovirus intron. Subcellular-fractionation and sucrose-gradient analyses showed that most spliced IVS1Cbeta1 lariats cofractionated with pre-mRNA, but not always with mRNA in the nucleus. Some IVS1Cbeta1 also appeared to be selectively exported to the cytoplasm, whereas TCR-beta pre-mRNA remained in the nucleus. This study constitutes the first detailed analysis of the stability and fate of a spliced nuclear intron in vivo.  (+info)

(4/3508) Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.  (+info)

(5/3508) Immune response to the immunodominant epitope of mouse hepatitis virus is polyclonal, but functionally monospecific in C57Bl/6 mice.

Mutations in an immunodominant CD8 CTL epitope (S-510-518) are selected in mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus. These mutations abrogate recognition by T cells harvested from the infected CNS in direct ex vivo cytotoxicity assays. Previous reports have suggested that, in general, an oligoclonal, monospecific T cell response contributes to the selection of CTL escape mutants. Herein, we show that, in MHV-JHM-infected mice, the CD8 T cell response after intraperitoneal infection is polyclonal and diverse. This diverse response was shown to include both polyclonal and oligoclonal components. The polyclonal data were shown to fit a logarithmic distribution. With regard to specificity, we used a panel of peptide analogues of epitope S-510-518 and spleen-derived CD8 T cell lines to determine why only a subset of possible mutations was selected in persistently infected mice. At a given position in the epitope, the mutations identified in in vivo isolates were among those that resulted in the greatest loss of recognition. However, not all such mutations were selected, suggesting that additional factors must contribute to selection in vivo. By extrapolation of these results to the persistently infected CNS, they suggest that the selection of CTL escape mutants requires the presence of a monospecific T cell response but also show that this response need not be oligoclonal.  (+info)

(6/3508) Characterization of CD4+ CD8alphaalpha+ and CD4-CD8alphaalpha+ intestinal intraepithelial lymphocytes in rats.

Intestinal intraepithelial lymphocytes (i-IEL) of aged rats comprise CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ T cells expressing TCR alphabeta. In the present study, we compared characteristics between CD4+CD8alphaalpha+ and CD4-CD8alphaalpha+ i-IEL, which were purified by a cell sorter from the i-IEL of 6-month-old Lewis rats. Most of the CD4+CD8alphaalpha+ i-IEL were of the CD44(hlgh) phenotype, while CD4-CD8alphabeta+ i-IEL were CD44(low). Vbeta usage in the CD4-CD8alphaalpha+ i-IEL was much diversified, while CD4+CD8alphaalpha+ i-IEL showed a skewed Vbeta repertoire. The CD4+CD8alphaalpha+ i-IEL but not the CD4-CD8alphaalpha+ i-IEL proliferated in response to syngeneic spleen cells, which was partially inhibited by addition of anti-MHC class I mAb. The CD4+CD8alphaalpha+ i-IEL produced IFN-gamma and IL-2 but no IL-4 or transforming growth factor (TGF)-beta in response to syngeneic spleen cells, while CD4-CD8alphaalpha+ i-IEL produced abundant levels of TGF-beta but no IL-2, IFN-gamma or IL-4. CD4+CD8alphaalpha+ i-IEL proliferated in response to exogenous IL-2 but not to IL-15, while CD4-CD8alphaalpha+ i-IEL could respond to IL-15 as well as IL-2. These results suggest that a significant fraction of CD4+CD8alphaalpha+ i-IEL belongs to Th1-type T cells capable of responding to self-MHC class I, while CD4-CD8alphaalpha+ i-IEL are a unique population with a diversified Vbeta repertoire that respond to IL-15 in rats.  (+info)

(7/3508) Development and function of autospecific dual TCR+ T lymphocytes.

Recent studies have challenged the long held concept that each T lymphocyte expresses on its surface only a single, unique alphabetaTCR. Dual TCR+ T cells have been recognized, however, their origin and potential to escape screening for self-reactivity remain obscure. We now report the thymic generation of dual alphabetaTCR+ T cells in the H-2Db/H-Y-specific TCR transgenic (Tg) mouse. Dual TCR+ thymocytes were positively selected less efficiently than single TCR+ thymocytes, although a subset attained maturity. Importantly, when TCR Tg mice were bred onto a negatively selecting background, auto-specific cells survived central deletion and matured as CD4+ dual TCR+ cells. These cells were autoreactive when CD8 expression was restored. The existence of autospecific, dual TCR+ T cells may have implications for the maintenance of self tolerance.  (+info)

(8/3508) Crossreactive recognition of viral, self, and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes: implications for molecular mimicry in autoimmune disease.

The immunodominant, CD8(+) cytotoxic T lymphocyte (CTL) response to the HLA-B8-restricted peptide, RAKFKQLL, located in the Epstein-Barr virus immediate-early antigen, BZLF1, is characterized by a diverse T cell receptor (TCR) repertoire. Here, we show that this diversity can be partitioned on the basis of crossreactive cytotoxicity patterns involving the recognition of a self peptide-RSKFRQIV-located in a serine/threonine kinase and a bacterial peptide-RRKYKQII-located in Staphylococcus aureus replication initiation protein. Thus CTL clones that recognized the viral, self, and bacterial peptides expressed a highly restricted alphabeta TCR phenotype. The CTL clones that recognized viral and self peptides were more oligoclonal, whereas clones that strictly recognized the viral peptide displayed a diverse TCR profile. Interestingly, the self and bacterial peptides equally were substantially less effective than the cognate viral peptide in sensitizing target cell lysis, and also resulted only in a weak reactivation of memory CTLs in limiting dilution assays, whereas the cognate peptide was highly immunogenic. The described crossreactions show that human antiviral, CD8(+) CTL responses can be shaped by peptide ligands derived from autoantigens and environmental bacterial antigens, thereby providing a firm structural basis for molecular mimicry involving class I-restricted CTLs in the pathogenesis of autoimmune disease.  (+info)


  • T cell receptors recognize foreign antigens which have been processed as small peptides and bound to major histocompatibility complex (MHC) molecules at the surface of antigen presenting cells (APC). (
  • In cellular immunity, clonally distributed T cell receptors (TCRs) engage complexes of peptides bound to major histocompatibility complex proteins (pMHCs). (


  • By using gene transfer technologies, T cells can be genetically engineered to express a unique high-affinity T cell receptor (TCR) or a chimeric antigen receptor (CAR), both of which confer novel tumour antigen specificity. (
  • We ran computer simulations to test whether enrichment for specific VDJ H combinations could be detected in "antigen-exposed" populations, and found that enrichment is detectable with moderate-to-high sensitivity and high specificity, even when some VDJ H combinations are not represented at all in some test sets. (
  • Hence heavy chain VDJ (VDJ H ) segment usage is a major determinant of antigen specificity. (
  • Hence V(D)J segment choice and sequence-level modification provide coarse- and fine-tuning, respectively, for antigen specificity, but different V(D)J and sequence combinations may well bind the same antigen. (
  • These considerations and substantial experimental data (summarized in [ 4 ]) argue against a strict one-to-one relationship between antibody sequence and antigen specificity. (
  • A specificity comprises a single epitope, a set of epitopes on a single antigen, or a set of antigens. (


  • The TCR is associated with the CD3 complex (gamma, delta, epsilon and zeta chains) and upon TCR recognition of an HLA/peptide complex the CD3 chains that contain immunotyrosine-activating motifs mediate signal transduction in the T cell. (
  • A single amino acid residue, Gln136, located within the connecting peptide domain of Cbeta controls the ability of the alpha/beta TCR to transmit a full signal. (
  • TCRs are responsible for recognizing peptide antigens bound and "presented" by major histocompatibility complex (MHC) proteins. (
  • TCR recognition of a peptide/MHC complex (pMHC) drives the initiation and propagation of a cellular immune response as well as the development and maintenance of the T cell repertoire. (
  • Whereas antibodies can be elicited against antigens of nearly unlimited structural diversity, TCRs recognize a composite surface consisting of the antigenic peptide bound in a groove formed of flanking α helices and a β sheet floor (Figure 1A ). (
  • Reports also indicate that V beta 5+ T cells recognize the OVA peptide. (


  • Structurally, TCRs are similar to antibodies, comprising four immunoglobulin domains and an antigen binding site with complementarity determining region (CDR) loops generated through genetic recombination and nucleotide editing. (
  • However, TCRs and antibodies differ in the nature of the antigen they recognize. (
  • The patient's immune system fights back with killer T cells (CD8+ T cells) and B-cell-produced antibodies. (
  • To date several studies have sought to catalog the full suite of antibodies that humans naturally produce against single antigens or other specificities (repertoire). (
  • To date several studies have addressed this idea in particular instances by sequencing antibodies specific for particular antigens. (


  • T cell receptors (TCRs) are clonotypic membrane proteins on the surface of T cells. (


  • Using ex vivo gene transfer, T cells from patients can be genetically engineered to express a novel T cell receptor or chimeric antigen receptor to specifically recognize a tumour-associated antigen and thereby selectively kill tumour cells. (


  • In spite of their compromised antigen responsiveness, the mutant TCR complex contains the CD3-gamma, -delta, -epsilon, and -zeta chains, and undergoes zeta chain phosphorylation and ZAP-70 recruitment. (
  • 1 It binds to a heterodimeric receptor complex formed by TCCR/WSX-1 and gp130, a common receptor subunit shared by IL-6 family cytokines. (
  • Recent evidence suggests that the p28 subunit of IL-27 may form a second protein complex with cytokine-like factor 1 (CLF), which is also involved in regulating the balance between pro- and anti-inflammatory T cell responses. (
  • The protein encoded by this gene is the CD3-epsilon polypeptide, which together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T cell receptor-CD3 complex. (
  • This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. (


  • To examine whether filaggrin deficiency predisposes to skin inflammation and epicutaneous (EC) sensitization with protein antigen. (
  • Filaggrin deficient mice exhibit Th17-dominated skin inflammation, eczematous changes with age, and are permissive to EC sensitization with protein antigen. (
  • Several V and J segments of the alpha locus are known to be incapable of encoding a protein and are considered pseudogenes. (
  • TRAV19 (T-Cell Receptor Alpha Variable 19) is a Protein Coding gene. (


  • AD has been considered a Th2 mediated disease, characterized by elevated IgE and Th2 cytokine expression in acute skin lesions, Several recent observations suggest the presence of IL-17-producing cells infiltrating the dermis in acute AD lesions and in the peripheral blood of AD patients 5 , 6 . (
  • 3, 5 Despite its role in promoting Th1 differentiation, studies performed using TCCR/WSX-1-deficient mice infected with various pathogens suggest that IL-27 signaling is also required to prevent excessive T cell activity and limit pro-inflammatory cytokine production. (
  • IL-27 is a heterodimeric cytokine secreted by activated antigen-presenting cells. (


  • A growing body of evidence suggests that autoreactive CD8 T cells contribute to the disease process in multiple sclerosis (MS). Lymphocytes in MS plaques are biased toward the CD8 lineage, and MS patients harbor CD8 T cells specific for multiple central nervous system (CNS) antigens. (
  • The focus of this review is to highlight the current models of pathogenic CNS-reactive CD8 T cells and the molecular mechanisms these lymphocytes use when causing CNS inflammation and damage. (


  • Both the alpha and delta loci include V (variable), J (joining), and C (constant) segments and the delta locus also includes diversity (D) segments. (
  • However, due to technological limitations detailed information was lacking regarding the size of clonal expansions and the diversity of the TCR-repertoire in naive and memory T-cell populations. (


  • These characteristics were reminiscent of the phenotype of Tr1 cells, a subset of CD4 + FoxP3 +/- IL-10 + T regulatory (Treg) cells that expand in the presence of IL-2, suggesting that IL-27 may in part confer a Tr1-like activity on CD4 + T cells. (


  • How much variety of a TCR can be produced by TCR alpha and beta genes? (
  • Scientists currently do not know the reasons for the qualitative differences in the immune responses of different individuals during primary HIV infection, Dr. Fauci notes, but they probably include factors intrinsic to the HIV-infected person, such as the genes that encode specific markers called human leukocyte antigens (HLAs) on immune system cells. (


  • Recombination of many different V segments with several J segments provides a wide range of antigen recognition. (


  • The MR9-4 antibody recognizes the V beta 5.1 and 5.2 chains on T cells from mouse strains with the b haplotype of the Tcrb gene, including C57BL/6, B10, and C58/J. V beta 5.1 and 5.2 are deleted in mouse strains that express MHC Class II I-E, including Balb/c, C3H, and DBA/2. (


  • Upon antigen encounter a T-cell may proliferate to produce a clone of TCR-identical cells, which develop a memory phenotype. (


  • Addition of IL-2 to activated T cells significantly enhanced IL-27-induced IL-10 secretion, while a neutralizing antibody to IL-2 inhibited IL-10 production. (
  • Specifically, we ask whether the large-scale sequencing of antibody repertoires might provide a diagnostic tool for detecting antigen exposure. (
  • In each antibody, contact with the antigen is made by six short regions, three on each heavy and light chain. (
  • However, they do suggest the possibility that antigens may have signature antibody repertoires. (
  • This MR9-4 monoclonal antibody reacts with the mouse T cell receptor (TCR) V beta 5.1/5.2 chain. (


  • If both delta and gamma rearrangements produce functional chains, the cell expresses delta and gamma. (
  • Five variable segments can be used in either alpha or delta chains and are described by TRAV/DV symbols. (
  • Hybridomas expressing the wt TCR-α chain and wt or mutant β chains were stimulated with DAP.3-DR1-presenting cells and SEB as described in Fig. 2. (
  • In line with this observation we show that the beta-chains repertoire size of the CD4 memory compartment is only two times smaller, and that of the CD8 memory compartment is only 3-10 times smaller than the naive compartments. (
  • All T cells have receptors with alpha and beta chains, and on the beta chain is a region known as V-beta that varies among T cells. (


  • In accordance, the beta-chain repertoire of T-cell memory subsets was reported to be 10 times less diverse than those of naive subsets, reflecting stringent selection. (
  • Regardless of the amount of HIV in the blood during primary infection, patients who mobilized a broad repertoire of CD8+ T cells had slower progression of disease than individuals who showed a pronounced expansion of only a single subset of CD8+ T cells. (

immune system

  • The immune system is able to respond to millions of antigens using adaptive receptors, including the alpha beta-T-cell receptor (TCR). (
  • One important way in which a person's immune system responds to primary HIV infection is by mobilizing different subsets of certain white blood cells -- CD8+ T cells -- that can destroy cells that have been infected with HIV," says Dr. Fauci. (

epithelial cells

  • Medullary epithelial cells of the thymus express self antigens in the context of MHC I and II. (


  • Normal appearing skin from 8-week-old ft/ft mice had epidermal thickening and increased dermal infiltration with CD4 + cells and expression of mRNA for IL-17, IL-6 and IL-23, but not IL-4, IL-13 or IFN-γ. (



  • It is also mediated by Fas ligand, which induces apoptosis upon binding to its receptor Fas on target cells. (


  • Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. (


  • In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. (
  • who also found that IL-27 could induce the production of IL-10 and IFN-gamma, and inhibit IL-17 secretion by anti-CD3, anti-CD28-activated human CD4 + T cells. (


  • Humans have 24 different V-beta families. (


  • How is differentiation into a CD4 or CD8 positive T cell decided? (
  • In contrast, it inhibits inflammation by suppressing Th17 differentiation and inducing a T regulatory (Tr1)-like activity in differentiated Th1 and Th2 effector cells. (
  • IL-10 secretion by these cells has anti-inflammatory, immunosuppressive effects that may serve as a negative feedback mechanism to balance IL-27-induced Th1 differentiation. (


  • Human T-cell memory consists mainly of unexpanded clones[J]. IMMUNOLOGY LETTERS,2010,133(1):42-48. (


  • Four other patients had moderate expansions of one or two V-beta subsets. (



  • A cell surface receptor that signals a common lymphoid progenitor cell to differentiate into a T cell lineage and not a B cell one. (
  • It drives inflammation by promoting the early commitment of naïve CD4 + T cells to a Th1-specific lineage. (


  • Each of these cytokines consists of an alpha (p19, p28, or p35) and a beta (p40 or EBI3) chain and signals through receptors that are highly expressed on T cells and/or natural killer cells. (


  • However, the few studies that have been done characterizing the mechanisms used by CD8 T cells to induce CNS autoimmunity indicate that several of the paradigms of how CD4 T cells mediate CNS autoimmunity do not hold true for CD8 T cells or for patients with MS. Thus, myelin-specific CD4 T cells are likely to be one of several important mechanisms that drive CNS disease in MS patients. (


  • However, T cell therapies for cancer have so far been limited by the lack of ability to isolate and expand high-affinity T cells restricted to tumour-associated antigens and by the limited in vivo expansion. (
  • Currently, there are relatively few experimental model systems available to study these pathogenic CD8 T cells in vivo . (


  • T cell therapy may have a clinical advantage compared with conventional therapies because of the specific lysis of antigen-positive cells, leaving other tissues intact. (
  • Using human or mouse naïve CD4 + T cells cultured under Th17-inducing conditions, IL-27 was shown to inhibit expression of the Th17-specific transcription factor, RORgamma t, and subsequent secretion of IL-17A. (


  • The alpha chain is synthesized by recombination joining a single V segment with a J segment. (


  • The potential of therapeutic T cells to traffic to sites of disease, expand and persist following a single injection remains a major advantage compared with MAbs. (
  • Signaling efficiency of the T cell receptor controlled by a single amino acid in the beta chain constant region. (
  • Four of these 21 patients had major expansions of a single V-beta subset during primary infection. (


  • The TCR is a heterodimer formed by the pairing of an alpha chain and a beta chain. (


  • Understanding how CNS-reactive CD8 T cells escape tolerance induction and induce CNS autoimmunity is critical to our ability to propose and test new therapies for MS. (


  • In their research, Dr. Fauci and his team have carefully analyzed CD8+ T cells taken from patients during primary HIV infection, classifying the cells according to the variable (V) regions of their receptors. (


  • Our results show that the T-cell memory compartment has a very different distribution of clones than anticipated. (
  • Other patients mobilize a wider array of T cells, with many different V-beta families. (


  • This is mediated by perforins, which insert themselves in the plasma membrane of target cells and form pores through which granzymes can enter and induce apoptosis of target cells. (
  • La autofosforilación de PRKDC parece jugar un importante papel en la recombinación no homóloga y se piensa que induce un cambio conformacional que le permite a las enzimas que procesan los extremos, acceder a dichos extremos de los cortes producidos en la doble hebra de ADN. (


  • 2011 ). Within active MS lesions, the inflammatory immune cells are predominantly T cells and activated macrophages and microglia, and often form focal demyelinating plaques (Frohman et al. (


  • However, it has been limited by the ability to isolate and expand T cells restricted to tumour-associated antigens. (


  • Indeed, genetically engineered T cells have recently been successfully used for cancer treatment in a small number of patients. (
  • 2007 ). The targeting of the CNS by immune cells and the ensuing death of neuronal tissue causes a wide spectrum of disease pathologies in MS patients (Noseworthy et al. (
  • Previously, the NIAID team demonstrated that during primary infection, some HIV-infected patients have a marked expansion of a limited variety of T cells, representing very few V-beta families. (
  • At approximately one year, this group of patients had a mean CD4+ T cell count of 456/mm3. (
  • Thirteen patients had expansions of multiple V-beta families or no expansion at all. (
  • The mean CD4+ T cell count in this group of patients was 651/mm3 after approximately one year. (


  • demonstrated that IL-27 could suppress the development of IL-17-producing Th17 cells. (
  • The epsilon polypeptide plays an essential role in T-cell development. (