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.Antigens: Substances that are recognized by the immune system and induce an immune reaction.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.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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, 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.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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).Antigens, Viral: Substances elaborated by viruses that have antigenic activity.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.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.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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.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.Sialic Acid Binding Ig-like Lectin 2: A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.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.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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.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.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Mice, Inbred C57BLHistocompatibility 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.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.Mice, Inbred BALB CAntigens, 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.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.H-2 Antigens: The major group of transplantation antigens in the mouse.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.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.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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Epitopes: Sites on an antigen that interact with specific antibodies.Antigens, Fungal: Substances of fungal origin that have antigenic activity.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.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.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Immunoglobulin D: An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.Duffy Blood-Group System: A blood group consisting mainly of the antigens Fy(a) and Fy(b), determined by allelic genes, the frequency of which varies profoundly in different human groups; amorphic genes are common.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesAntigens, 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.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)Spleen: An encapsulated lymphatic organ through which venous blood filters.Proto-Oncogene Proteins c-vav: Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.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.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).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.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.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.src Homology Domains: Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.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.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.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.PhosphoproteinsImmunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.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.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.Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.GRB2 Adaptor Protein: A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.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.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.Immunoglobulin alpha-Chains: The class of heavy chains found in IMMUNOGLOBULIN A. They have a molecular weight of approximately 58 kDa and contain about 470 amino acid residues arranged in four domains and an oligosaccharide component bound covalently to their Fc fragment constant region.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Enzyme-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.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.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.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.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.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, 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.Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.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.Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.B-Lymphocyte Subsets: A classification of B-lymphocytes based on structurally or functionally different populations of cells.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.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.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)Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.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.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.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.Protein Tyrosine Phosphatase, Non-Receptor Type 6: A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.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.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.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.Immunological Synapses: The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.Cross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.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.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.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.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).Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.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.Burkitt Lymphoma: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.Molecular Weight: The sum of the weight of all the atoms in a molecule.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Palatine Tonsil: A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the PHARYNX. There is one on each side of the oropharynx in the fauces between the anterior and posterior pillars of the SOFT PALATE.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.Kinetics: The rate dynamics in chemical or physical systems.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.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.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.NFATC Transcription Factors: A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.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.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.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.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Genes, Immunoglobulin: Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Models, Immunological: Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.GPI-Linked Proteins: A subclass of lipid-linked proteins that contain a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE which holds them to the CELL MEMBRANE.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Antigens, CD1d: A major histocompatibily complex class I-like protein that plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Dual Specificity Phosphatase 3: A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES.Nitrohydroxyiodophenylacetate: Also called 4-hydroxy-3-iodo-5-nitrophenylacetate. A haptenic determinant that can be radiolabeled and used as salts and derivatives for investigations of immunogenic specificity studies.Immunoglobulin mu-Chains: The class of heavy chains found in IMMUNOGLOBULIN M. They have a molecular weight of approximately 72 kDa and they contain about 57 amino acid residues arranged in five domains and have more oligosaccharide branches and a higher carbohydrate content than the heavy chains of IMMUNOGLOBULIN G.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Lymphoma, B-Cell: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.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.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.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).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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Proto-Oncogene Proteins c-cbl: Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.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.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.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.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)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.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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Membrane Microdomains: Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
  • The term extranodal natural killer/T-cell lymphoma (NKTCL) refers to a group of clonal proliferations of cytotoxic lymphocytes of natural killer (NK) or, more rarely, T-cell types, with peculiar clinicopathologic features, arising mainly as tumors or destructive lesions in the nasal cavity, maxillary sinuses, or palate [ 1 ]. (hindawi.com)
  • The cell of origin of these tumors has been debated. (hindawi.com)
  • Extranodal NKTCL represents the major group of mature NK cell neoplasms in the recently revised WHO classification of hematolymphoid tumors, which also include the aggressive NK cell leukemia (ANKL) and a provisional group of chronic NK-cell lymphoproliferative disorder of uncertain malignant potential, most likely related to T-cell large granular lymphomas [ 1 ]. (hindawi.com)
  • We observed that fewer NK cells infiltrated the tumors in IFN-γ receptor knockout (IFN-γR −/− ) mice compared with wild-type controls that correlated with decreased survival rate. (aacrjournals.org)
  • Our results identify IFN-γ and the expression of CXCR3 on NK cells as prerequisites for NK cell infiltration into tumors. (aacrjournals.org)
  • For this reason, it is important to identify and exploit factors regulating NK cell accumulation in tumors to improve the success of antitumor therapies. (aacrjournals.org)
  • Therefore, NK cells are particularly important for the elimination of tumors with reduced or absent MHC class I expression that evade CD8 + T cell-mediated killing ( 15 ). (aacrjournals.org)
  • Thus far, only little is known about chemokines or other factors governing accumulation of NK cells in tumors and tumor metastases. (aacrjournals.org)
  • T-cell receptor γ δ T cells constitute an important subset of cytotoxic non-conventional effectors involved in immune reactions against mycobacteria and tumors. (haematologica.org)
  • In the resistant tumors, TAMs remained inactive and did not exert antigen-presenting activity. (jci.org)
  • Seven days after the last administration, splenocytes were isolated and restimulated with peptides of predicted neoepitopes or known tumor antigens (AH-1 in CT26 and NY-ESO-1 p81 in CMS5a/NY tumors). (jci.org)
  • Moreover, we found that hyaluronan fragments constitute a common factor produced by various tumors to induce the formation of immunosuppressive Mφ, and also that upregulation of hyaluronan synthase-2 in tumor cells is correlated with the ability of the cells to cause Mφ dysfunction. (bloodjournal.org)
  • Malignant gliomas express tumor-associated and tumor-specific antigens that should make these tumors detectable to the immune system ( 1 ). (aacrjournals.org)
  • On the contrary, killing of different NK-susceptible tumor cell lines was variably affected, reflecting the differential usage of NKp30 and/or NKG2D in the lysis of such tumors. (pnas.org)
  • One of this markers, the paraneoplastic antigen Ma2 (PNMA2), which is normally expressed only in nervous tissue, can in the process of carcinogenesis be detected in tumors located outside the nervous system. (enets.org)
  • used a three-dimensional, collagen-fibrin gel system to investigate the effects of CD8 + T cells on cocultured melanoma cells excised from mouse tumors. (sciencemag.org)
  • APUDOMA is a general term collectively applied to tumors associated with APUD cells. (slicksurface.com)
  • To investigate the impact of CTL therapy on the cell cycle of tumor cells in situ , we generated B16 cells expressing a fluorescent ubiquitination-based cell-cycle indicator (B16-fucci) and performed CTL therapy in mice bearing B16-fucci tumors. (aacrjournals.org)
  • The immune system protects against assaults on the body External assaults include microorganisms: protozoans, bacteria, and viruses Internal assaults: abnormal cells reproduce and form tumors that may become cancerous and spread. (slideserve.com)
  • In seeing the promise of CAR T-cell immunotherapy, Seattle Children's researchers are also working to develop CAR T-cell trials that will target solid tumors, including brain tumors and sarcomas. (eurekalert.org)
  • Refuge initially focused on furthering cell therapy efficacy in solid tumors, but now we are exploring the potential ways to utilize the Refuge platform beyond oncology indications. (wuxiapptec.com)
  • Upon activation, CD8 + T cells develop into cytolytic T lymphocytes (CTLs) ready to kill cells infected by intracellular pathogens, such as viruses, or eradicate tumors cells. (biology-online.org)
  • Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. (springer.com)
  • This review discusses the mechanisms and potential therapeutic applications of antigen-specific T cell tolerance techniques using syngeneic apoptotic cellular carriers and synthetic nanoparticles that are covalently cross-linked to diabetogenic peptides or proteins through ethylene carbodiimide (ECDI) to prevent and treat T1D. (soc-bdr.org)
  • A range of cells and proteins are deployed to neutralise or destroy pathogens. (cjswaby.com)
  • Sneaky and resourceful little chaps, they can also team up with other proteins to form traps for pathogens outside of cells. (cjswaby.com)
  • These T cells are primed to recognize foreign proteins expressed on malignant and non-self cells. (haematologica.org)
  • Zymosan, an immune stimulator, is composed of a crude mixture of yeast cell wall materials including proteins, lipids, and polysaccharides synthesized into a drug, which unfortunately has many negative side effects in patients. (betaglucan.org)
  • With the PLAT-05 trial, researchers will now be able to reprogram CAR T cells to detect and destroy leukemia cells by targeting both the CD19 and CD22 proteins upfront. (eurekalert.org)
  • These diverse biological roles are due to the tendency of CD81 to associate with other tetraspanins and with cell-specific partner proteins, which provide the cells with a signaling platform. (stanford.edu)
  • Fig. 5: 19BBz CAR-T cells are effective against RS4;11 GFP+ tumor cells in vivo. (nature.com)
  • Here, using a B16 melanoma tumor model expressing the tumor surrogate antigen chicken albumin (OVA), we show that tumor antigen specific CD4+ T cells are rendered anergic in vivo through a mechanism that requires NFAT1 activity and involves the expression of anergy specific genes. (aacrjournals.org)
  • Specifically, corneal endothelial cells cannot proliferate in vivo. (arvojournals.org)
  • Characteristics of cancer-initiating cells also include high levels of the antiapoptotic genes, the ability to form neurospheres, nonadherence, possession of marker characteristics for astrocytic, neuronal, and oligodendroglial lineages ( 16 ), and tumorigencity in vivo . (aacrjournals.org)
  • By using IC-loaded DCs, ovalbumin (OVA)-specific CD4 + and CD8 + T cells have been successfully induced in mice ( 8 ), suggesting that effective cross-presentation also occurs in vivo . (pnas.org)
  • Examples include ex vivo gene transfer to modify cells, which are then infused into patients as described in "Gene Transfer and T-cell Therapies for Viral Infection and Cancer" and in the accompanying article by Aiuti and Roncarolo, beginning on page 678, and by local injection of vectors directly into sites with highly circumscribed anatomy, such as the retina. (pubmedcentralcanada.ca)
  • This presents a substantial challenge to translating advances in our understanding of Treg biology into immunotherapy for human type 1 diabetes, because the literature on the natural repertoire of human islet antigen-specific Tregs that may contribute to the tolerant state in vivo is scant. (diabetesjournals.org)
  • In recent years, we have developed approaches that allow the functional interrogation of human autoreactive T-cells directly ex vivo for their ability to respond to islet autoantigens ( 14 , 15 ). (diabetesjournals.org)
  • T cells and natural killer cells are both thought to be important in the graft- versus -leukemia effect, and both cell types are amenable to ex vivo manipulation and clinical manufacture, making them versatile immunotherapeutics. (haematologica.org)
  • 9 From a therapeutic perspective, both cell types are amenable to ex vivo manipulation and clinical manufacture, thus making them versatile immunotherapeutics. (haematologica.org)
  • Compared to other cells, both T cells and NK cells are amenable to ex vivo manipulation, making them excellent sources of biological therapeutics. (haematologica.org)
  • Ex vivo , these NS3-1073-specific CD8 + T cells were found to be both naive and memory cells. (asm.org)
  • These data suggest that VEGF, at pathologically relevant concentrations in vivo, may exert effects on pluripotent stem cells that result in blocked DC development as well as affect many other hematopoietic lineages. (bloodjournal.org)
  • We ask in this study whether recombinant VEGF alone at relevant concentrations would cause significant alterations in DC development in vivo in otherwise healthy animals, which cell populations would be most affected, and what role other factors may play in the effects mediated by VEGF. (bloodjournal.org)
  • The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective. (patentsencyclopedia.com)
  • Delayed-type hypersensitivity response (DTH) is a rapid in vivo manifestation of T cell-dependent immune response to a foreign antigen (Ag) that the host immune system has experienced in the recent past. (jove.com)
  • Comparative analysis of ex vivo Nrp1 + and Nrp1 - Tfh cells reveals gene expression modulation during activation. (plos.org)
  • WuXi AppTec communications asked Dr. Wang to explain how Refuge's unique cell therapy platform can fight cancer in vivo and the future benefits of and challenges in developing cell therapies. (wuxiapptec.com)
  • IFN-gamma can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen. (springer.com)
  • This ability is dependent on an efficient means of exposing the cells to antigenic peptides, achieved through a mechanism known as antigen presentation. (uio.no)
  • Importantly, recognition of various peptides derived from unrelated viruses by NS3-1073-specific CD8 + T cells showed a considerable degree of T cell cross-reactivity, suggesting that they might in part originate from previous heterologous infections. (asm.org)
  • We describe here a strategy to identify helper T-cell epitopes for HER2/neu that focuses on peptides predicted to bind to numerous histocompatibility alleles (promiscuous epitopes), which would encourage their use in therapeutic vaccines for the general cancer patient population. (unboundmedicine.com)
  • Interestingly, one of these peptides, HER2(883), was recognized by T cells in the context of either HLA-DR1, HLA-DR4, HLA-DR52, and HLA-DR53, indicating a high degree of histocompatibility promiscuity. (unboundmedicine.com)
  • Several mechanisms have been proposed to account for the anergic phenotype of tumor antigen-specific T cells. (aacrjournals.org)
  • 4 , 5 The M2 cells share an IL-12 low /IL-10 high phenotype and are generally better adapted to remodeling tissues. (bloodjournal.org)
  • Tumor-derived factors, including IL-10 and transforming growth factor (TGF)-β1, "educate" the newly recruited monocytes to take on a M2 phenotype and perform a protumoral role. (bloodjournal.org)
  • On the contrary, in certain pathological conditions, such as acute myeloid leukemia (AML), most patients' NK cells were found to express a homogeneous NCR dull phenotype ( 9 ). (pnas.org)
  • Langerhans cells ( 7 ) and lymph node (LN) CD11c + cells from influenza-infected mice can express functional FasL ( 8 ), yet the precise phenotype of FasL + DC was not reported in the latter study. (jimmunol.org)
  • D. A. MacKenzie, J. Schartner, J. Lin, A. Timmel, M. Jennens-Clough, C. G. Fathman, C. M. Seroogy, GRAIL is up-regulated in CD4 + CD25 + T regulatory cells and is sufficient for conversion of T cells to a regulatory phenotype. (sciencemag.org)
  • However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. (wjgnet.com)
  • Murine fibrosarcoma CMS5a is highly refractory to checkpoint inhibition and lacks a specific CD8 + T cell response. (jci.org)
  • A ) The murine tumor cell line CT26, CMS7, CMS5a/NY, or CMS5a was subcutaneously inoculated into BALB/c mice. (jci.org)
  • The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. (jcancer.org)
  • We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-β. (jcancer.org)
  • CD45 does not colocalize with lipid rafts on murine and human non-transformed hematopoietic cells, but CD45 positioning within lipid rafts is modified during their oncogenic transformation to acute myeloid leukemia. (wikipedia.org)
  • Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an lptA mutant of strain FA19 induced significantly lower levels of NF-κB in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. (asm.org)
  • In a murine model of hematopoietic stem cell transplantation, CAR-modified Tregs were more effective in preventing the development of graft-versus-host disease compared with polyclonal Tregs. (jci.org)
  • Natural CD4 + CD25 + regulatory T cells (nT regs ) have proven highly effective in preventing GVHD and autoimmunity in murine models. (sciencemag.org)
  • To understand global effector mechanisms of CTL therapy, we performed microarray gene expression analysis in a murine model using pmel-1 T-cell receptor (TCR) transgenic T cells as effectors and B16 melanoma cells as targets. (aacrjournals.org)
  • In addition, CD8 + T cells and NK cells are essential to the control of murine cytomegalovirus (MCMV) replication ( 33 ). (asm.org)
  • Here we report that the key T-cell transcription factor NFAT mediates expression of anergy-associated genes in the context of cancer. (aacrjournals.org)
  • Mice whose genes for T-bet have been "knocked-out" lack Th1 cells and have elevated numbers of Th2 cells (making them susceptible to such Th2-mediated disorders as asthma ). (biology-pages.info)
  • Ninety-two genes/sequences were differentially expressed in adenocarcinomas and/or squamous cell carcinomas compared with their corresponding normal tissues. (aacrjournals.org)
  • Several genes discovered recently of which the functions are unknown, such as KIAA0728 and KIAA0425 , were also differentially expressed in both adenocarcinomas and squamous cell carcinomas of the lung. (aacrjournals.org)
  • Vitamin D with the vitamin D receptor (VDR) binds to the regulatory sequences in the promoters of p21 and p27 genes activating their transcription that leads to the inhibition of the CDKs, lack of Rb phosphorylation and inhibition of the cell cycle progression. (intechopen.com)
  • The adaptive immune system depends on the ability to assemble rearranged genes for both the T-cell receptor (TCR) and the immunoglobulin gene. (diabetesjournals.org)
  • We have previously identified six novel marker genes for neuroendocrine tumor cells by using Affymetrix microarrays and advanced bioinformatics. (enets.org)
  • Diaz M, Velez J, Singh M, Cerny J and Flajnik MF (1999) Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation. (els.net)
  • Papavasiliou FN and Schatz DG (2000) Cell‐cycle‐regulated DNA double‐stranded breaks in somatic hypermutation of immunoglobulin genes. (els.net)
  • Refuge's technology enables cells to sense their surroundings and conditionally activate or repress multiple genes when they encounter specific external antigens. (wuxiapptec.com)
  • In particular, with receptor-dCas, immune cells can now be engineered to conditionally turn on/off certain genes, such as PD-1, to generate more potent CAR-T immune cells when it senses the presence of a tumor cell. (wuxiapptec.com)
  • Refuge is uniquely positioned to be able to tackle these issues together as its platform technology has the ability to target multiple pathways that underpin these mechanisms at the same time by modulating multiple genes simultaneously in addition to a cell therapy itself, such as CAR-T. This effectively designs an intelligent cell that is fitter and can react to its environment. (wuxiapptec.com)
  • Over the last few years technological advances have made it possible to study, in parallel, the expression of thousands of genes in cells, tissues or organisms. (biology-online.org)
  • Our study aimed at identifying factors controlling intratumoral NK cell accumulation in s.c. injected NK cell sensitive tumor models and at studying their effect on survival time of recipient mice. (aacrjournals.org)
  • Accordingly, significantly lower numbers of tumor-infiltrating NK cells were detected in CXCR3 −/− mice, and the capacity of adoptively transferred CXCR3 −/− NK cells to accumulate in the tumor was severely impaired. (aacrjournals.org)
  • Stimulation of splenocytes from naive mice of differing genetic backgrounds with anti-CD3epsilon mAb resulted in significant production of TNF-alpha by naive CD8 T cells within 5 h. (umassmed.edu)
  • B ) The experiment was performed in nude mice as described in A . ( C and D ) Induction of a tumor-specific CD8 + T cell response by checkpoint inhibition was evaluated. (jci.org)
  • Indeed, cryopreserved donor nT regs restimulated four times significantly reduced GVHD lethality induced by the infusion of human T cells into immune-deficient mice. (sciencemag.org)
  • Lines have been developed using several different strains of mice. (slicksurface.com)
  • Ratios of interleukin (IL)-17 to interferon-gamma production were higher in antigen-driven cultures of splenocytes from severely arthritic mice compared to mildly or nonarthritic mice. (biomedcentral.com)
  • The ability of transferred CDPs to contribute to the pDC population in PP and to respond to Flt3L was evaluated by flow cytometry of PP single cell suspensions from recipient mice. (jove.com)
  • No differences in ACF formation were observed between CB1 receptor-deficient and wild-type mice. (420magazine.com)
  • Whereas the cells of the innate arm recognizes threats based on certain characteristics common to most invaders, adaptive immune cells is able to recognize billions of unique antigens due to specialized receptors on their surface. (uio.no)
  • This explains how the immune system is able to recognize and respond to a virtually inestimable number of foreign antigens. (diabetesjournals.org)
  • Of note, all Vγ9/Vδ2 T cells recognize the same small microbial compound ( E )-4-hydroxy-3-methyl-but-2-enyl pyrophosphate ( HMB-PP ), a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate (IPP) biosynthesis. (wikidoc.org)
  • In addition, many of the clones generated may not produce mAbs that recognize the antigen of interest. (justia.com)
  • Certain chemokine receptors, including CCR2 ( 18 ), CCR5 ( 19 ), CXCR3 ( 9 ), and CX3CR1 ( 20 ), were described to direct NK cells to sites of inflammation. (aacrjournals.org)
  • To date, there are more than 50 chemokines and 18 chemokine receptors identified [ 6 ]. (mdpi.com)
  • These cells, designated Treg , are discussed on another page. (biology-pages.info)
  • DO11 GRAIL cells also had larger amounts of the surface Treg markers, CD25, GITR, and CTLA4. (sciencemag.org)
  • In mouse, Nrp1 is expressed by recent thymic emigrant invariant NKT cells [ 18 ] and is constitutively expressed by natural Foxp3 + Treg cells [ 19 - 23 ]. (plos.org)
  • However, in humans Nrp1 expression is rarely found on CD25 + Foxp3 + Treg cells [ 24 , 25 ]. (plos.org)
  • In turn, Treg cells hinder DCs and/or normal CD4+ T cells in their activities, while Th17 cells are involved in inflammatory and autoimmune reactions . (nih.gov)
  • However, there are no reports on the generation of genome integration-free and completely exogenous gene-silenced (footprint free) ciPSCs that are tolerant to enzymatic single-cell passage. (stanford.edu)
  • The natural mechanisms involved in host defense can turn against self, promoting the development of an autoimmune response to antigens of the host's own tissue. (diabetesjournals.org)
  • In summary, when the macrophage is activated by receptor contact with a beta glucan particulate, a cascade of events transforms the cells into 'an arsenal of defense,' according to Dr. Czop. (betaglucan.org)
  • Divided into granulocytes (N, E, B) and mononuclear cells (M, L). Responsible for defense against infections. (brainscape.com)
  • With this more robust defense, researchers hope the new experimental therapy, first being investigated in the phase 1 Pediatric Leukemia Adoptive Therapy (PLAT-05) trial, will ultimately be able to cut the rate of relapse following CAR T-cell therapy by almost half. (eurekalert.org)
  • One of the effects reported to occur in the tumor microenvironment is the induction of antigen-specific tolerance in CD4+ and CD8+ T cells ( 6, 7 ). (aacrjournals.org)
  • The immune system is a major player in the cancer cell/tumor microenvironment crosstalk. (biomedcentral.com)
  • But when the enemy is a solid tumor, one must do battle in the tumor microenvironment, a hostile terrain where one's allies in the immune system may lose their way, exhaust themselves, or even switch sides, lending cancer cells aid and comfort. (genengnews.com)
  • Dr. Bing Wang: As research progresses further into how cell therapies work and act within the tumor microenvironment, it is expected that better control over these mechanisms will improve the efficacy of cell therapies. (wuxiapptec.com)
  • More than structural cells, fibroblasts create and orchestrate the tumor microenvironment. (springer.com)
  • To address this, we developed a novel biomaterial therapy to deliver immunomodulatory agents along with autoantigen as a means to recruit and tolerize dendritic cells (DCs) for robust antigen-specific T cell tolerance ( 20 , 21 ). (frontiersin.org)
  • The capacity of the cells to generate antigen-specific CD8 T cell lines was initially validated using a recombinant canarypox virus expressing a defined immunodominant T. parva antigen (Tp1). (biomedcentral.com)
  • These lines were BHV-1-specific and class I MHC-restricted. (biomedcentral.com)
  • Given the relatively low frequencies of virus-specific CD8 T cells in circulating memory T cell populations (typically ranging from 1/500 to 1/20 000 in human peripheral blood) [ 8 , 9 ], such assays have limited sensitivity. (biomedcentral.com)
  • Several models of intrinsic T-cell hyporesponsiveness have been proposed, each regulated by a specific set of molecular mechanisms that maintain T cells anergic ( 10, 11 ). (aacrjournals.org)
  • By using CD40 activated B cells as an alternative APC, we observed a significant difference in T cell expansions towards specific antigens. (uio.no)
  • This stimulation also led to an increase in epitope specific cells against a known melanoma antigen, MART-1. (uio.no)
  • Although further investigations are needed, exploiting NK cell cytolysis and natural fragmentation of tumor associated antigens may hold utility in the development of cancer vaccines by providing new insights into tumor specific epitopes and neo-antigens. (uio.no)
  • The ability to tolerize T cells specific for autoantigens, allergens, and alloantigens remains the most desired treatment for a myriad of immune-mediated diseases, including autoimmune diseases such as type 1 diabetes (T1D). (soc-bdr.org)
  • A goal was to establish cell-type-specific expression of key transporters and enzymes involved in neurotransmitter metabolism in order to estimate neurotransmitter and metabolite traffic between neurons and astrocytes. (academicconcepts.net)
  • Blockade of GITRL did not affect allo-specific ACAID but led to infiltration of Foxp3(−)CD4 + T cells and allograft rejection. (arvojournals.org)
  • 23. The TCR of claim 16, wherein the TCR recognizes a specific antigen. (google.com.au)
  • The vitamin D receptor (VDR) with vitamin D (VD) binds as a heterodimer with the retinoid X receptor (RXR) specific sequence in the promoter region of the target gene - the vitamin D responsive element (VDRE). (intechopen.com)
  • CONCLUSIONS This hitherto undescribed population of islet autoantigen-specific Tregs displays unique characteristics that offer exquisite specificity and control over the potential for pathological autoreactivity and may provide a suitable target with which to strengthen β-cell-specific tolerance. (diabetesjournals.org)
  • Critically, these studies highlighted the importance of antigen specificity: islet-specific Tregs have far greater potency than those derived from polyclonal populations. (diabetesjournals.org)
  • These assassins directly attack and destroy other cells with the same specific antigen presented, this is done through various mechanisms. (cjswaby.com)
  • Among these, the NK-specific NKp46, NKp30, and NKp44, collectively termed natural cytotoxicity receptors (NCR) ( 5 ), and NKG2D ( 6 , 7 ) appear to play a major role in the NK-mediated cytotoxicity. (pnas.org)
  • Thus, their simultaneous blocking by specific mAbs results in the virtual abrogation of the NK-mediated cytolytic activity against the majority of target cells. (pnas.org)
  • 5 Over the last several decades, the introduction of calcineurin inhibitors, T-cell depletion strategies, and immunomodulators has helped to prevent GVHD, but at a cost - with inhibition of the donor-specific immune response including the graft-versus-tumor/leukemia (GVL) effect. (haematologica.org)
  • We performed a detailed characterization of CD8 + T cells specific to a hepatitis C virus (HCV) epitope (NS3-1073) in 121 HCV-seronegative individuals. (asm.org)
  • Research at Harvard University in the 1980s by Joyce Czop, Ph.D., found specific receptor sites for beta glucan that matches a site on the surface of the macrophage. (betaglucan.org)
  • The Harvard University research demonstrated the macrophage, an immune system white blood cell that 'eats' or subjects non-self foreign microbes to phagocytosis, has a specific receptor for beta-1,3-glucan approximately one micron in size. (betaglucan.org)
  • Confirmation of the direct killing effect of B cells on T cells was demonstrated using an antigen-specific T hybridoma cell line. (biomedcentral.com)
  • However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. (biomedcentral.com)
  • An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer. (biomedcentral.com)
  • HPV specific CD4+ T cells were generated using either a MHC class I or MHC class II restricted TCR (from clones A9 and 24.101 respectively) directed against HPV16 antigens. (biomedcentral.com)
  • Adoptive transfer of HPV specific T cells could be an attractive strategy to treat patients suffering from HPV induced malignancies. (biomedcentral.com)
  • Our studies provide a potentially more efficient approach for generating antigen-specific CTLs for ACT-based therapies and facilitate the development of therapeutic strategies for diseases. (jove.com)
  • The methods may be used to improve the efficiency of obtaining immortalized antigen-specific plasma cells or to improve the quality of molecularly cloned Ig heavy and light chains. (justia.com)
  • For a given target, dozens of mAbs may need to be screened, and thus the techniques used to generate the mAbs must be able to generate a panel of highly diverse antigen-specific (Ag-specific) mAbs. (justia.com)
  • Typically, one hybridoma clone may be generated per 10 5 -10 6 splenocytes fused, thus most of the Ag-specific cells contained within the splenocyte population may be lost. (justia.com)
  • The frequency of producing successful, Ag-specific B cell hybridomas may be on the order of one per 10 6 -10 8 starting cells. (justia.com)
  • Company-sponsored studies that are part of the Iovance clinical pipeline include an early Phase I trial for chronic lymphocytic leukemia and Phase II clinical trials for malignant melanoma, cervical cancer, head and neck cancers, and non-small-cell lung cancer. (genengnews.com)
  • Specifically, we utilized 30 µm MPs to provide local sustained release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor β1 (TGF-β1) along with 1 µm MPs to facilitate phagocytic uptake of encapsulated antigen and 1α,25(OH) 2 Vitamin D 3 (VD3) followed by tolerogenic antigen presentation. (frontiersin.org)
  • Remarkably, this IFN-γ-inducible characteristic was due neither to enhanced antigen uptake nor to facilitated antigen processing in LCs. (pnas.org)
  • The enhanced cross-presentation reflects, at least in part, the efficient uptake of IC-bound antigen by means of plasma membrane Fcγ receptors ( 5 , 7 , 8 ). (pnas.org)
  • Such interactions determine the extent of the cellular nanoparticles uptake in targeted drug delivery - shape and size have the potential to increase uptake into a desired cell type while minimizing the uptake into the other cell types14. (bioskinrevive.com)
  • acts as a positive-feedback device promoting more pre-Th cells to enter the Th2 pathway. (biology-pages.info)
  • The STAT3 pathway is constitutively active in these clones and the immunosuppressive properties were markedly diminished when the STAT3 pathway was blocked in the cancer-initiating cells. (aacrjournals.org)
  • These findings indicate that cancer-initiating cells contribute to the immune evasion of GBM and that blockade of the STAT3 pathway has therapeutic potential. (aacrjournals.org)
  • To develop a vaccine strategy by using IC, it is essential to understand the mechanism of antigen transport from the membrane to the cytosol by means of the cross-presentation pathway in DCs, which remains to be elucidated. (pnas.org)
  • Results of previous studies demonstrated that phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway may be activated in the great majority of NET cells. (enets.org)
  • It enhances tumor immunogenicity by upregulating components of the MHC antigen processing and presentation pathway. (aacrjournals.org)
  • Bacterial species that lack the non-mevalonate pathway and synthesize IPP via the classical mevalonate pathway instead, such as Streptococcus , Staphylococcus , and Borrelia , are unable to produce HMB-PP and do not specifically activate Vγ9/Vδ2 T cells. (wikidoc.org)