Receptors, KIR2DL2: A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL1 RECEPTORS and the KIR2DL3 RECEPTORS.Receptors, KIR3DL1: A KIR receptor that has specificity for HLA-B ANTIGENS. It is an inhibitory receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.Receptors, KIR3DL2: A KIR receptor that has specificity for HLA-A3 ANTIGEN. It is an inhibitory receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.Receptors, KIR3DS1: An activating KIR receptor that contains D0, D1, and D2 extracellular immunoglobulin-like domains and a short cytoplasmic tail.Receptors, KIR2DL4: A KIR receptor that has specificity for HLA-G antigen. It contains D0 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail.Receptors, KIR2DL1: A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL2 RECEPTOR and the KIR2DL3 RECEPTORS.HLA-C Antigens: Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).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.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Receptors, KIR: A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells.Receptors, KIR2DL3: A KIR receptor that has specificity for HLA-C ANTIGEN. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL2 RECEPTORS and the KIR2DL3 RECEPTORS.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, 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.Pre-B Cell Receptors: Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Receptors, KIR2DL5: An inhibitory KIR receptor that contains D0 and D1 extracellular immunoglobulin-like domains and a long cytoplasmic tail.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.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, 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).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.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).Receptors, Natural Killer Cell: Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.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.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.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.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.Complementarity Determining Regions: Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.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)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.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.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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Genes, T-Cell Receptor alpha: DNA sequences encoding the alpha chain of the T-cell receptor. The genomic organization of the TcR alpha genes is essentially the same in all species and is similar to the organization of Ig genes.Mice, Inbred C57BLT-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.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.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.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.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.Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.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.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)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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Gene Rearrangement, delta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors.Lectins, C-Type: A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.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.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.Immunoglobulin Light Chains, Surrogate: An immunolglobulin light chain-like protein composed of an IMMUNOGLOBULIN VARIABLE REGION-like peptide (such as light chain like lambda5 peptide) and an IMMUNOGLOBULIN CONSTANT REGION-like peptide (such as Vpreb1 peptide). Surrogate light chains associate with MU IMMUNOGLOBULIN HEAVY CHAINS in place of a conventional immunoglobulin light chains to form pre-B cell receptors.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.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.NK Cell Lectin-Like Receptor Subfamily D: A subclass of NK cell lectin-like receptors that associates with a variety of members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY C to form heterodimeric receptors for HLA-E antigen.NK Cell Lectin-Like Receptor Subfamily C: A subclass of NK cell lectin-like receptors that associates with members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY D to form heterodimeric receptors for HLA-E antigen.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.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.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.G Protein-Coupled Inwardly-Rectifying Potassium Channels: A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.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.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.Antibodies, Monoclonal: Antibodies produced by a single clone 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.Antigens: Substances that are recognized by the immune system and induce an immune reaction.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.H-2 Antigens: The major group of transplantation antigens in the mouse.Mice, Inbred BALB CMembrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.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.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.Genes, T-Cell Receptor delta: DNA sequences encoding the delta chain of the T-cell receptor. The delta-chain locus is located entirely within the alpha-chain locus.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.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 enzymesReceptors, NK Cell Lectin-Like: Structurally-related receptors that are typically found on NATURAL KILLER CELLS. They are considered lectin-like proteins in that they share sequence homology with the carbohydrate binding domains of C-TYPE LECTINS. They differ from classical C-type lectins, however, in that they appear to lack CALCIUM-binding domains.B-Lymphocyte Subsets: A classification of B-lymphocytes based on structurally or functionally different populations of cells.Genes, RAG-1: Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.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.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.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-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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Antigens, Ly: A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.Self Tolerance: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions.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.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.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.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.Epitopes: Sites on an antigen that interact with specific antibodies.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.NK Cell Lectin-Like Receptor Subfamily A: An inhibitory subclass of NK cell lectin-like receptors that interacts with CLASS I MAJOR HISTOCOMPATIBILITY ANTIGENS and prevents the activation of NK CELLS.Minor Lymphocyte Stimulatory Antigens: Endogenous superantigens responsible for inducing strong proliferative responses in T-cells in mixed lymphocyte reactions (see LYMPHOCYTE CULTURE TEST, MIXED). They are encoded by mouse mammary tumor viruses that have integrated into the germ line as DNA proviruses (MINOR LYMPHOCYTE STIMULATORY LOCI).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)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.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.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.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.Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.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.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.Genes, T-Cell Receptor gamma: DNA sequences encoding the gamma chain of the T-cell receptor. The human gamma-chain locus is organized similarly to the TcR beta-chain locus.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.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.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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.Receptors, Virus: Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Immunogenetic Phenomena: GENETIC PHENOMENA characterizing IMMUNITY and the immune response.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.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.Gene Rearrangement, B-Lymphocyte: Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.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.Membrane Microdomains: Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.Clonal Anergy: Functional inactivation of T- or B-lymphocytes rendering them incapable of eliciting an immune response to antigen. This occurs through different mechanisms in the two kinds of lymphocytes and can contribute to SELF TOLERANCE.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.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.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Precursor Cells, B-Lymphoid: Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.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.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.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)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.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.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.Clonal Deletion: Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.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.Myelin Basic Protein: An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.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.NK Cell Lectin-Like Receptor Subfamily B: A subclass of NK cell lectin-like receptors that includes both inhibitory and stimulatory members.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.Kinetics: The rate dynamics in chemical or physical systems.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.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).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).Histocompatibility Antigen H-2D: A component of the murine major histocompatibility complex class I family. It contains one Ig-like C1-type domain and functions in processing and presentation of exogenous peptide antigens to the immune system.Receptors, Interleukin-2: Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.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.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.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).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.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.Gene Rearrangement, B-Lymphocyte, Light Chain: Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.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.VDJ Recombinases: Recombinases involved in the rearrangement of immunity-related GENES such as IMMUNOGLOBULIN GENES and T-CELL RECEPTOR GENES.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).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.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.Natural Killer T-Cells: A specialized subset of T-LYMPHOCYTES that exhibit features of INNATE IMMUNITY similar to that of NATURAL KILLER CELLS. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D ANTIGEN.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).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.PhosphoproteinsTime Factors: Elements of limited time intervals, contributing to particular results or situations.Immunoglobulin Joining Region: A segment of the immunoglobulin heavy chains, encoded by the IMMUNOGLOBULIN HEAVY CHAIN GENES in the J segment where, during the maturation of B-LYMPHOCYTES; the gene segment for the variable region upstream is joined to a constant region gene segment downstream. The exact position of joining of the two gene segments is variable and contributes to ANTIBODY DIVERSITY. It is distinguished from the IMMUNOGLOBULIN J CHAINS; a separate polypeptide that serves as a linkage piece in polymeric IGA or IGM.Lymphocyte Count: The number of LYMPHOCYTES per unit volume of BLOOD.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.Mice, Inbred AKRMembrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).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.Mice, Inbred DBADNA: 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).Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells.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.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.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.HLA-DR1 Antigen: An HLA-DR antigen associated with HLA-DRB1 CHAINS that are encoded by DRB1*01 alleles.Mice, Inbred CBAEpitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
1efx: STRUCTURE OF A COMPLEX BETWEEN THE HUMAN NATURAL KILLER CELL RECEPTOR KIR2DL2 AND A CLASS I MHC LIGAND HLA-CW3 ... On the cell surface, these proteins are bound to protein fragments (peptides) that have been exported from within the cell. MHC ... 2fyy: The role of T cell receptor alpha genes in directing human MHC restriction ... 2fz3: The role of T cell receptor alpha genes in directing human MHC restriction ...
Killer-cell immunoglobulin-like receptor
... and all KIR receptors share more than 90% sequence identity. two domains, long cytoplasmic tail: KIR2DL1, KIR2DL2, KIR2DL3, ... Because natural killer cells target virally infected host cells and tumor cells, inhibitory KIR receptors are important in ... The co-expression of many MHC-specific receptors by NK cells is disfavored, likely because cells that co-express receptors are ... KIR3DS1 NK cell receptors bind directly to the MHC class I molecules on the surface of target cells. Human killer cell ...
Examples include antibodies, the giant muscle kinase titin, and receptor tyrosine kinases. Immunoglobulin-like domains may be ... Williams AF, Barclay AN (1988). "The immunoglobulin superfamily-domains for cell surface recognition". Annu. Rev. Immunol. 6: ... IGSF11 IGSF2 IGSF21 IGSF3 IGSF9 IL11RA IL1R1 IL1R2 IL1RAPL1 IL1RAPL2 IL1RL1 IL1RL2 IL6R JAM2 JAM3 KIR-123FM KIR2DL1 KIR2DL2 ... Brümmendorf T, Rathjen FG (1995). "Cell adhesion molecules 1: immunoglobulin superfamily". Protein Profile. 2 (9): 963-1108. ...
Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... T cells expressing this receptor are referred to as α:β (or αβ) T cells, though a minority of T cells express an alternate ... The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes, that is responsible for ... On helper T cells and regulatory T cells, this co-receptor is CD4 that is specific for MHC class II. ...
Outline of immunology
T cells Antigen receptor - T cell receptor (TCR) Subunits - [email protected] / [email protected] / [email protected] / [email protected] Co-receptors CD8 (CD8α / CD8β) CD4 ... Killer inhibitory receptors (KIRs) Two domains, long cytoplasmic tail KIR2DL1 KIR2DL2 KIR2DL3 KIR2DL4 KIR2DL5A KIR2DL5B Two ... Commonly termed CD4+ T cells Th1 cells Th2 cells Th3 cells Th17 cells TFH cells - Follicular helper T cells Cytotoxic T cells ... Lymphoid cells B cells Plasma B cells Memory B cells B-1 cells B-2 cells (the conventional B cells most texts refer to) ...
MHC class I
Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... The α3-CD8 interaction holds the MHC I molecule in place while the T cell receptor (TCR) on the surface of the cytotoxic T cell ... Paired-immunoglobulin-like receptor B (PirB), an MHCI-binding receptor, is involved in the regulation of visual plasticity. ... The α3 domain is plasma membrane-spanning and interacts with the CD8 co-receptor of T-cells. ...
Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... "Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells". J Exp Med. 158 (4): 1092-113. ... CD64 (Cluster of Differentiation 64) is a type of integral membrane glycoprotein known as an Fc receptor that binds monomeric ... Ernst L, van de Winkel J, Chiu I, Anderson C (1992). "Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI ...
... complement receptors, Fc receptors, B cell receptors and T cell receptors. ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 . Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... Steroid and thyroid-hormone receptors are examples of such receptors.. Membrane receptors may be isolated from cell ...
Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... This affinity keeps the T cell receptor of the cytotoxic T cell and the target cell bound closely together during antigen- ... CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). ... Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell antigen interactions ...
Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... enzyme linked receptor protein signaling pathway. • entry into host cell. • T cell activation. • positive regulation of T cell ... T cell differentiation. • cell surface receptor signaling pathway. • positive regulation of T cell proliferation. • positive ... CD4 is a co-receptor of the T cell receptor (TCR) and assists the latter in communicating with antigen-presenting cells. The ...
റിസപ്റ്റർ (ജൈവരസതന്ത്രം) - വിക്കിപീഡിയ
Cytokine receptor. *see cytokine receptors. Killer-cell IG-like receptors. *KIR2DL1. *KIR2DL2 ... An example of membrane receptors. *Ligands, located outside the cell. *Ligands connect to specific receptor proteins based on ... Wikipedia:MeSH D12.776#MeSH D12.776.543.750 - receptors.2C cell surface. അവലംബം[തിരുത്തുക]. *↑ Hall, JE (2016). Guyton and Hall ... The receptor releases a messenger once the ligand has connected to the receptor. ...
Glikoprotein 130 - Википедија, слободна енциклопедија
1989). „Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130.". Cell. 58 (3): 573-81 ... KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3 ... 1992). „CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor ... An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells". ...
"The Journal of Cell Biology 152 (3): 435-450. PMC 2195998. PMID 11157973. doi:10.1083/jcb.152.3.435. More than one of ,number= ... KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3 ... Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A ... G protein-spregnuti receptor (Hedgehog, Wnt) • RTK (TGF beta, MAPK/ERK) • Notch • JAK-STAT • Akt/PKB • Fas apoptoza • Hippo • ...
KIR2DL2: Killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2
GoPubMed lists recent and important papers and reviews for killer cell immunoglobulin-like receptor, two domains, long ... The results are the first direct proof of the implication of KIR2DL2 receptor in the control of natural killer cell activation ... Here we report the crystal structure of the human immunoglobulin-like NK cell receptor KIR2DL2 in complex with its class I ... Killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2. KIR2DL2, p58.2 ...
Receptors, KIR2DL2 | Profiles RNS
Receptors, Cell Surface [D12.776.543.750]. *Receptors, Immunologic [D12.776.543.750.705]. *Receptors, Natural Killer Cell [ ... KIR2DL2" by people in this website by year, and whether "Receptors, KIR2DL2" was a major or minor topic of these publications. ... "Receptors, KIR2DL2" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... A KIR receptor that has specificity for HLA-C ANTIGENS. It is an inhibitory receptor that contains D1 and D2 extracellular ...
SCOPe 2.02: Structural Classification of Proteins - extended
Compound: natural killer cell receptor kir2dl2. Species: Homo sapiens [TaxId:9606]. Database cross-references and differences ( ... Compound: natural killer cell receptor kir2dl2. Species: Homo sapiens [TaxId:9606]. Database cross-references and differences ( ... Description: structure of a complex between the human natural killer cell receptor kir2dl2 and a class I MHC ligand hla-cw3. ... Keywords: MHC, HLA, class I, KIR, NK cell receptor, Immunoglobulin fold, receptor/MHC complex, IMMUNE SYSTEM. Deposited on 2000 ...
Frontiers | Protein Kinase C-θ (PKC-θ) in Natural Killer Cell Function and Anti-Tumor Immunity | Immunology
... while others show that it is implicated in NK cell functional activation mediated by certain killer activating receptors (KAR ... Natural killer (NK) cells, which express PKCtheta, play a prominent role in this process, mainly by elimination of tumor cells ... Natural killer (NK) cells, which express PKCtheta, play a prominent role in this process, mainly by elimination of tumor cells ... while others show that it is implicated in NK cell functional activation mediated by certain killer activating receptors (KAR ...
HEADER IMMUNE SYSTEM 10-FEB-00 1EFX TITLE STRUCTURE OF A COMPLEX BETWEEN THE HUMAN NATURAL KILLER TITLE 2 CELL RECEPTOR KIR2DL2 ... NATURAL KILLER CELL RECEPTOR KIR2DL2; COMPND 19 CHAIN: D, E; COMPND 20 FRAGMENT: EXTRACELLULAR D1 AND D2 DOMAINS; COMPND 21 ... 1 TITL 2 KILLER CELL INHIBITORY RECEPTOR KIR2DL2 REMARK 1 REF PROC.NATL.ACAD.SCI.USA V. 96 3864 1999 REMARK 1 REFN ISSN 0027- ... NK CELL RECEPTOR, IMMUNOGLOBULIN KEYWDS 2 FOLD, RECEPTOR/MHC COMPLEX, IMMUNE SYSTEM EXPDTA X-RAY DIFFRACTION AUTHOR J.C. ...
Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age...
Our findings also suggest an important role of natural killer cells (or other ,i ,KIR,/i,-expressing cells) in the progress of ... To investigate whether killer cell immunoglobulin-like receptor ,i ,(KIR),/i, and human leukocyte antigen ,i ,(HLA),/i, genetic ... However, since there is little biologic difference between KIR2DL2 and KIR2DL3 (KIR2DL2 and KIR2DL3 are alleles of the same ... "Killer-cell immunoglobulin-like receptor genotyping and HLA killer-cell immunoglobulin-like receptor-ligand identification by ...
HLA-B - Wikipedia
1efx: STRUCTURE OF A COMPLEX BETWEEN THE HUMAN NATURAL KILLER CELL RECEPTOR KIR2DL2 AND A CLASS I MHC LIGAND HLA-CW3 ... On the cell surface, these proteins are bound to protein fragments (peptides) that have been exported from within the cell. MHC ... 2fyy: The role of T cell receptor alpha genes in directing human MHC restriction ... 2fz3: The role of T cell receptor alpha genes in directing human MHC restriction ...
Interactions of NK Cell Receptor KIR3DL1*004 with Chaperones and Conformation-Specific Antibody Reveal a Functional Folded...
Several unfolded variants of KIR2DL2 and KIR2DS receptors have also been described (69, 72, 73). It would now be of interest to ... On human NK cells, the killer cell Ig-like receptor (KIR) family of receptors can both inhibit and activate the NK cell ... In contrast, in cells expressing KIR3DL1*004, green GFP tagging the receptor was visible inside the cell, wheras red labeling ... First, in the effector phase of NK cell activity, a low amount of inhibitory receptor could make the NK cell more readily ...
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence | JEM
Crystal structure of the HLA-Cw3 allotype-specific killer cell inhibitory receptor KIR2DL2. Proc. Natl. Acad. Sci. USA. 96:3864 ... The cell biology of the human natural killer cell CD94/NKG2A inhibitory receptor. Mol. Immunol. 42:485-488. ... NK cell receptors of the orangutan (Pongo pygmaeus): a pivotal species for tracking the coevolution of killer cell Ig-like ... MHC-Ia molecules are recognized by the NK receptors of the Ig superfamily, killer cell Ig-like receptors (KIRs) (2) and Ig-like ...
CD158b (KIR2DL2/DL3) Antibody, anti-human, REAfinity™ - Recombinant antibodies - MACS Antibodies - Products - Miltenyi Biotec -...
... members of the killer immunoglobulin-like receptor (KIR) family expressed on natural killer (NK) cells and subsets of T cells. ... KIRs contribute to the regulation of NK cell-mediated cytotoxicity and possess high allelic polymorphism with either 2 or 3 Ig- ... CD158b provides an inhibitory signal on NK cell lytic activity upon interaction with HLA C (e.g. alleles HLA-Cw1, HLA-Cw3, HLA- ... Cw7) in an antigen-independent manner.Additional information: Clone REA1006 displays negligible binding to Fc receptors. - ...
Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high...
... as their only inhibitory receptor for self, a KIR for which there was no class I ligand in the recipient. KIR2DL2/3/S2 single- ... Donor NK-cell purification. (A) Flow cytometric analysis of NK cells after T-cell depletion and after CD56+ cell positive ... NK cells. Thus, a median of 2.74 × 106 CD3−CD56+ cells/kg (range, 1.11-5 × 106 CD3−CD56+ cells/kg) were infused. NK-cell ... 4 NK cells possess clonally distributed inhibitory receptors termed killer cell immunoglobulin-like receptors (KIRs) that ...
Phenotypic and Functional Characterization of NK Cells in Human Immune Response against the Dimorphic Fungus Paracoccidioides...
We also showed that NK cells from PCM patients exhibited a higher expression of the inhibitory receptors KIR2DL2/L3/S2 and ... The percentage of CD56+ cells [NK cells (CD56+CD3− cells) or NKT cells (CD56+CD3+ cells)] was similar in peripheral blood of ... against K562 cells (used as target cells). Several target cell (K562 cell)/effector cell proportions (1:1, 1:3, 1:7, 1:15, 1:30 ... The recognition of target cells by NK cells is made by several stimulatory and inhibitory receptors expressed by NK cells and ...
Tipifarnib in Subjects With Myelodysplastic Syndromes - Full Text View - ClinicalTrials.gov
Killer-cell immunoglobulin-like receptor - Wikipedia
... and all KIR receptors share more than 90% sequence identity. two domains, long cytoplasmic tail: KIR2DL1, KIR2DL2, KIR2DL3, ... Because natural killer cells target virally infected host cells and tumor cells, inhibitory KIR receptors are important in ... The co-expression of many MHC-specific receptors by NK cells is disfavored, likely because cells that co-express receptors are ... KIR3DS1 NK cell receptors bind directly to the MHC class I molecules on the surface of target cells. Human killer cell ...
Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex. - PubMed - NCBI
... conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2- ... Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I ... Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.. Fan QR1, Long EO, Wiley DC. ... We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to ...
rs12979860 - SNPedia
Diversity of Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes and KIR2DL2/3 Variants in HCV Treatment Outcome ... Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with ... PMID 24224717] Genetic variation in toll-like receptors and retinoic acid-inducible gene I and outcome of hepatitis C virus ... PMID 23121365] IL28B genetic variation and hepatitis C virus-specific CD4(+) T-cell responses in anti-HCV-positive blood donors ...
De Novo Expression of Killer Immunoglobulin-Like Receptors and Signaling Proteins Regulates the Cytotoxic Function of CD4 T...
Gene expression was confirmed by cell-surface staining for CD158b/j, which recognizes gene products of KIR2DS2, KIR2DL2, and ... T-cell clones to lyse target cells on crosslinking of the T-cell receptor (Figure 6B). In wild-type transduced T-cell clones, ... In contrast to CD4+CD28+ T cells, CD4+CD28null T cells possess perforin/granzyme granules and, on T-cell receptor triggering, ... DAP12- and WT-infected T-cell clones killed on T-cell receptor triggering (▴). In the absence of DAP12, T-cell clones were ...
Frontiers | Quantifying the Protection of Activating and Inhibiting NK Cell Receptors during Infection with a CMV-Like Virus |...
... which allow NK cells to screen the cellular health of target cells. Although these inhibitory receptor-ligand interactions have ... which allow NK cells to screen the cellular health of target cells. Although these inhibitory receptor-ligand interactions have ... Many studies have demonstrated that CMV infection can be controlled by NK cells via their activating receptors, but the exact ... Many studies have demonstrated that CMV infection can be controlled by NK cells via their activating receptors, but the exact ...
Expression of KIR2DL1 on the entire NK cell population: a possible novel immunodeficiency syndrome | Blood Journal
Expression of other NK receptors, including KIR2DL2, KIR3DL1, NKG2A, CEACAM1, LIR1, and NKp46, was normal (28%, 21%, 25%, 12%, ... Expression of killer cell inhibitory receptors on human uterine natural killer cells. Eur J Immunol. 1997;27: 979-983. ... 2 It was suggested that such diversity of NK receptors enables the killing of infected cells by at least a subset of NK cells.3 ... Expression of KIR2DL1 receptor was detected on all NK cells in the bulk culture, by the HP3E4 or the EB6 monoclonal antibodies ...
NK Cells in Mucosal Defense against Infection
This in combination with recognition of infected cells by activating receptors (Ly49 mouse, KIR human, NKp both) on NK cells ... of lung resident NK cells express KIRs including KIR2DL2, KIR2DL3, KIR3DL1 and KIR2DS2. Nearly 80% of the population expressed ... NK cells in the murine intestinal mucosa also appear immature. IEL and LP NK cells of naïve mice are and , respectively [32-34 ... NK cells found in the gut mucosa and FRT during the naive state exhibit an immature phenotype being in mice and CD16− in humans ...
A66900, CD158b1/b2,j-PC5.5 Conjugated Antibody, GL183, 0.5 mL, ASR - Beckman Coulter
... these acronyms stand for Killer cell Immunoglobulin (Ig)-like Receptor (KIR), with extracellular part containing 2 Ig Domains ( ... They are expressed by a subset of NK cells, and can be detected on the surface of sub-populations of peripheral T lymphocytes, ... CD158b1/b2 (p58.2/p58.3) function as inhibitory receptors for a group of HLA-C molecules (Cw1, Cw3, Cw7 and Cw8 supertypes). ... There is another comprehensive nomenclature which refers to these molecules as KIR2DL2 for CD158b1 (p58.2), KIR2DL3 for CD158b2 ...
Clinical grade ex vivo expanded human natural killer (NK) cells - English
NK cells. NK-cell doses in this trial will range from 5 ) cytotoxicity, as CD158b/KIR2DL2/3, KIR3DL1 and 106 to 108 NK cells/kg ... Surface expression of the NK-cell inhibitory receptor CD158b increased in expanded NK cells; compared with fresh NK cells, the ... cells was significantly higher with expanded NK cells T cells, no CD56/CD3 cells, no CD19 B cells and (27.699.3%) compared with ... TM-LCL feeder cells at a 10:1 feeder to NK cell ratio at DTM under resting non-expanded NK cells against K562 and RCC cell GMP ...
Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African...
... and higher CD4+ T-cell counts(+80 cells/μl;SE = 42;p = 0.04). This was largely explained by the protective effect of KIR2DL2/ ... Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in ... and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for ... Killer-cell Immunoglobulin-like Receptors(KIR) interact with Human Leukocyte Antigen(HLA) to modify natural killer- ...
Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus...
We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We ... Our data suggests that KIR 2DL2 has a protective role in EVD; similarly, this gene is protective against HIV-1 and HCV ... class I molecules on target cells and receptors, such as the killer cell immunoglobulin-like receptors (KIRs), on NK cells (15 ... Activating and inhibitory receptors of natural killer cells. Immunol Cell Biol. 2011;89:216-24. DOIPubMed ...
Increased frequencies of the killer immunoglobulin-like receptor genes KIR2DL2 and KIR2DS2 are associated with neuroblastoma. ...
... cells are innate lymphocytes that are known to mediate the direct cytotoxicity of neuroblastoma tumour cells. Natural variation ... Increased frequencies of the killer immunoglobulin-like receptor genes KIR2DL2 and KIR2DS2 are associated with neuroblastoma.. ... We found a significant increase in the frequency of KIR2DL2 (P = 0.019) as well as KIR2DS2 (P = 0.008) in patients with ... Natural Killer Cell Research Group, School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College ...
Genetic and Environmental Determinants of Human NK Cell Diversity Revealed by Mass Cytometry | Science Translational Medicine
We next restricted the Boolean analysis to the six inhibitory NK cell receptors KIR2DL1, KIR2DL2/L3/S2, KIR2DL5, KIR3DL1, NKG2A ... nodes of phenotypically similar cell clusters corresponding to NK cells, CD4+ T cells, CD8+ T cells, B cells, and monocytes/ ... NK cell receptor coexpression patterns. We next asked whether any single NK cell receptors were more likely to be expressed ... cells lacking receptors for self-HLA are hyporesponsive to HLA-deficient target cells (52), uneducated cells can be effective ...
The D0 Domain of KIR3D Acts as a Major Histocompatibility Complex Class I Binding Enhancer | JEM
Crystal structure of the HLA-Cw3 allotype-specific killer cell inhibitory receptor KIR2DL2. Proc. Natl. Acad. Sci. USA. 96:3864 ... A particular diverse family of NK cell receptors is the killer cell Ig-like receptors (KIR).* KIR have either two (KIR2D) or ... killer cell immunoglobulin-like receptor with two Ig-like domains; KIR2DS, killer cell immunoglobulin-like receptor with two Ig ... killer cell immunoglobulin-like receptor with three Ig-like domains; KIR3DL, killer cell immunoglobulin-like receptor with ...
Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility | Genes & Immunity
... are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding ... Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort (P=0.030 and ... the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. ... with the appropriate human leucocyte antigen (HLA) ligand on target cells. Recent genetic association studies have implicated ...
A New Approach for Quantitative Phosphoproteomic Dissection of Signaling Pathways Applied to T Cell Receptor Activation |...
Recently, certain KIRs (KIR2DL2 and KLRG1) have been shown to disrupt late T cell receptor-stimulated effector functions such ... to T-cell antigen receptor-mediated signaling: reconstitution studies of a PLC-gamma1-deficient Jurkat T-cell line. Mol. Cell. ... 2004) Jurkat T cells and development of the T-cell receptor signaling paradigm. Nat. Rev. Immunol. 4, 301-308 ... T cell receptor. Zap-70. zeta-chain-associated protein kinase 70. ITIM. immunoreceptor, the tyrosine-based inhibitory motif. ...
SMART: IG domain annotation
STRUCTURE OF A COMPLEX BETWEEN THE HUMAN NATURAL KILLER CELL RECEPTOR KIR2DL2 AND A CLASS I MHC LIGAND HLA-CW3. ... Ig-like domains are involved in a variety of functions, including cell-cell recognition, cell-surface receptors, muscle ... Human Fc-gamma-Receptor IIa (FcgRIIa), monoclinic. 1hkf. The three dimensional structure of NK cell receptor Nkp44, a ... INHIBITORY RECEPTOR (P58-CL42) FOR HUMAN NATURAL KILLER CELLS. 1npu. CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF MURINE PD ...
KIR2DS2CytotoxicityImmunoglobulin-like receptorLectin-like receptorGenotypeLeukocyteImmunePolymorphicMOLECULEInhibitionSubsets2DS2Expression of inhibitoryAntigensNKG2ALymphocytesInteractionAbility of NK cellsProteinsNatural killePeptidesSubsetFrequencyActivationCytokinesPhenotypeAbsenceAllelesInteractsSignalsEffectorLysisSurfaceTumor cellLong cytoplasmic tailLyseGlycoproteinKiller inhibitory
- We found a significant increase in the frequency of KIR2DL2 (P = 0.019) as well as KIR2DS2 (P = 0.008) in patients with neuroblastoma compared with the healthy control group. (cdc.gov)
- The activating receptor KIR2DS2 and the inhibitory receptor KIR2DL2 were more frequently found in AD patients than controls, and they were found at similar frequencies (62% of AD patients vs. 37.2% of controls, and 62.2% of AD patients vs. 36.4% of controls, respectively). (hhv-6foundation.org)
- These two receptors are likely preferentially associated with each other, and when they are co-expressed, the inhibitory effects of KIR2DL2 override the activation of NK cells triggered by KIR2DS2. (hhv-6foundation.org)
- The combination of KIR2DS2, KIR2DL2, and the KIR ligand HLA-C1 was observed significantly more often among AD patients, and the presence of HLA-C1 in the absence of KIR2DS2 and KIR2DL2 was markedly lower than in controls. (hhv-6foundation.org)
- The group also evaluated HHV-6A infection in the presence of KIR2DL2 expressing cells to determine whether the KIR2DS2/KIR2DL2/C1 combination might increase a person's susceptibility to HHV-6 infections. (hhv-6foundation.org)
- The diminished ability of KIR2DS2/KIR2DL2 expressing NK cells to clear HHV-6-infected cells with HLA-C1 present, paired with the increased frequency of this KIR/HLA combination among AD patients, suggests that underlying genetic factors may predispose to ineffective clearance of HHV-6(A). Consequently, HHV-6 infections may persist in the central nervous system and contribute to AD development and worsening. (hhv-6foundation.org)
- Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. (gopubmed.org)
- Natural killer cells are important mediators of cytotoxicity and cytokine secretion in innate immunity. (jimmunol.org)
- NK cells are able directly to recognize and kill P. brasiliensis yeast cells, and this activity seems to be granule-dependent but perforin-independent, whereas the cytotoxicity against P. brasiliensis -infected monocytes is perforin-dependent. (jimmunol.org)
- Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. (nih.gov)
- Natural killer (NK) cells are innate lymphocytes that are known to mediate the direct cytotoxicity of neuroblastoma tumour cells. (cdc.gov)
- There is a need to use HIV-infected primary T-cell blasts as target cells rather then infected-T-cell lines in the cytotoxicity assays. (jove.com)
- During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B. (genome.jp)
- Upon binding of HLA ligand, KIR molecules regulate cytotoxicity and cytokine production through balanced control of activation and inhibition of NK cells. (ragoninstitute.org)
- At the end of the 21-28 day culture period, CD3 + CD56 + cells, derived from CD3 + CD56 - cells, acquire cytotoxicity against various tumour cell targets, including acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), B and T-cell lymphoma. (biomedcentral.com)
- These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. (aacrjournals.org)
- These fully human or humanized mAbs are either of the IgG 4 isotype, which does not mediate antibody-dependent cell-mediated cytotoxicity (ADCC), or of the IgG 1 isotype and specifically engineered to eliminate ADCC activity. (aacrjournals.org)
- Furthermore, HHV-6A induced PKA activity and phosphorylation of Sp1 in the NK cells, which may increase expression of KIR2DL2 and thereby inhibit NK cell cytotoxicity. (hhv-6foundation.org)
- NK cells are effector cells of the innate immune system that recognize the absence of HLA class I molecules from the surface of virally infected cells and target these cells for destruction through cytotoxicity and pro-inflammatory cytokine production1 (Figure 2). (chori.org)
- Any process that modulates the frequency, rate, or extent of natural killer cell mediated cytotoxicity. (princeton.edu)
- Effector functions of NK cells include direct natural cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), as well as secretion of inflammatory cytokines and chemokines that indirectly regulate the functions of other immune cells 2 , 3 . (jcancer.org)
- They are, 1) killer immunoglobulin like receptors (KIR), 2) NKG2A-C that form a heterodimer with CD94, and NKG2D, which is expressed as a homodimer and relies on DAP10 and DAP12 adaptor proteins, and 3) natural cytotoxicity receptors (NCR) ( Table 1 ). (jcancer.org)
- The equilibrium of signaling through activating and inhibitory receptors dictates whether a given NK cell will execute cellular cytotoxicity. (jci.org)
- The resulting NKG2A null NK cells had higher cytotoxicity against HLA-E-expressing tumor cells. (jci.org)
- Transduction of anti-NKG2A PEBL produced more potent cytotoxicity than interference with an anti-NKG2A antibody and prevented de novo NKG2A expression without affecting NK cell proliferation. (jci.org)
- GWI patients demonstrated impaired immune function as demonstrated by decreased NK cytotoxicity and altered gene expression associated with NK cell function. (biomedcentral.com)
- We determined the capacity of the leukemia cell line K562 modified to express a membrane-bound form of interleukin (IL)-15 and 41BB ligand (K562-mb15-41BBL) to generate human NK cells with enhanced cytotoxicity. (aacrjournals.org)
- This notion is corroborated by the observation that, among patients with leukemia undergoing hematopoietic stem cell transplantation, the antileukemic effect of the transplant was significantly greater when the donor NK cells exhibited a killer inhibitory receptor (KIR) profile that predicted a higher cytotoxicity against the leukemic cells of the recipient ( 3 , 5 - 7 ). (aacrjournals.org)
- In this study, we determined the capacity of NK cells stimulated by contact with K562-mb15-41BBL cells to exert anti-AML cytotoxicity. (aacrjournals.org)
- Methods and agents such as monoclonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided. (patentsencyclopedia.com)
- NK cells are mainly known for their cytolytic function, but recent work indicates that strong KIR/HLA interactions that induce NK "licensing" augment NK cytotoxicity but also IFN-γ production. (caltech.edu)
- Killer cell immunoglobulin-like receptor gene association with cryptorchidism. (gopubmed.org)
- Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms. (gopubmed.org)
- To investigate whether killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) genetic background could influence the onset age of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection, one hundred and seventy-one males with HBV-related HCC were enrolled. (hindawi.com)
- range, 53-73 years) received highly purified CD56 + CD3 − natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. (bloodjournal.org)
- Members of the IgSF family include the human killer cell immunoglobulin-like receptor (KIR) and the Immunoglobulin-like transcripts (ILT). (wikipedia.org)
- CD4 + CD28 null T cells variably express receptors of the killer immunoglobulin-like receptor (KIR) family. (ahajournals.org)
- The killer immunoglobulin-like receptor (KIR) family recognizes class I major histocompatibility complex (MHC) molecules and inhibits natural killer (NK) activity. (bloodjournal.org)
- Concordantly, variation in the Human Leukocyte Antigen (HLA) and Killer-cell Immunoglobulin-like Receptor (KIR) loci, the two most polymorphic regions of the human genome that encode receptors involved in NK and CD8+ T-cell function, is associated with rates of HIV disease progression across several studies [ 2 ]. (biomedcentral.com)
- To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. (sciencemag.org)
- The killer immunoglobulin-like receptor ( KIR ) gene family is located within the IBD6 linkage region at chromosome 19q13.4. (nature.com)
- Killer cell immunoglobulin-like receptor (KIR) gene-content variation in the HGDP-CEPH populations. (chori.org)
- High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles. (chori.org)
- Identification of novel killer cell immunoglobulin-like receptor (KIR) alleles is a testament to the genetic diversity in this population. (ac.ke)
- The family of KIR (killer-cell immunoglobulin-like receptor) interacts with HLA class I molecules, especially those HLA-C alleles in-group 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 and C*16) by activating or inhibiting the function of these cells. (bvsalud.org)
- Studies examining ESNs or slow progressors linked the beneficial effect with certain key features of NK cell activation, the killer immunoglobulin-like receptor (KIR) on NK cells and its ligand the human leukocyte antigen-class I molecules (HLA) on the target cells. (biomedcentral.com)
- Currently published studies investigating association between the killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and rheumatoid arthritis (RA) reported inconsistent and contradictory results. (biomedcentral.com)
- After isolating genomic DNA from the whole blood of 98 AD patients, the genotype of NK killer Ig-like receptors (KIR) was examined. (hhv-6foundation.org)
- Notably, 14/20 patients who exhibited worsening of clinical manifestations at one -year follow-up possessed this combination of NK receptors and HLA genotype, and the combination was also associated with significantly lower Mini-Mental State Examination scores at diagnosis of AD. (hhv-6foundation.org)
- NK cells from carriers of the *h/*y + B*57 genotype have higher NK cell functional potential and inhibit HIV replication in autologous HIV-infected CD4+ T cells (iCD4) more potently than those from carriers of non-protective genotypes. (biomedcentral.com)
- The second KIR3DS1 homozygous protective genotype encodes an activating receptor that upon interacting with its HLA-F ligand on iCD4 induces anti-viral activity. (biomedcentral.com)
- Their function is governed, at least in part, by the combinatorial array of inhibitory and activating receptors including the KIR, Leukocyte immunoglobulin-like receptors (LILR), the C-type lectin receptors-NKG2A-F, and the natural cytotoxic receptors (NCRs) -NKp30, NKp44 and NKp46. (biomedcentral.com)
- Genetic epistasis between killer immunoglobulin-like receptors and human leukocyte antigens in Kawasaki disease susceptibility. (gopubmed.org)
- The protein kinase C-θ (PKCθ), which is essential for T cell function and survival, is also required for efficient anti-tumor immune surveillance. (frontiersin.org)
- Recent data offer some clues on the mechanism that could explain the important role of PKCθ in NK cell-mediated anti-tumor immune surveillance: some studies show that PKCθ is implicated in signal transduction and anti-tumoral activity of NK cells elicited by interleukin (IL)-12 or IL-15, while others show that it is implicated in NK cell functional activation mediated by certain killer-activating receptors. (frontiersin.org)
- Alternatively, the possibility that PKCθ is involved in NK cell degranulation is discussed, since recent data indicate that it is implicated in microtubule-organizing center polarization to the immune synapse in CD4 + T cells. (frontiersin.org)
- One of them, Fas Ligand (FasL), is also implicated in immune homeostasis maintenance through activation-induced cell death (AICD). (frontiersin.org)
- The appearance of clinically detectable tumors may be the result of the proliferation of cells that have developed sophisticated strategies to escape the immune response. (frontiersin.org)
- If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by destroying the infected cell. (wikipedia.org)
- They also influence the adaptive immune response by secreting immunoregulatory cytokines that stimulate T cells and dendritic cells ( 1 , 2 ). (jimmunol.org)
- Natural killer (NK) cells are a type of lymphocyte cell involved in the innate immune system's response to viral infection and tumor transformation of host cells. (wikipedia.org)
- Like T cells, NK cells have many qualities characteristic of the adaptive immune system, including the production of "memory" cells that persist following encounter with antigens and the ability to create a secondary recall response. (wikipedia.org)
- Besides their role in fighting viral infection and tumor resistance, recent studies have shown that NK cells also participate in the immune response against other infectious diseases. (jimmunol.org)
- The aim of this study was to characterize the possible role of NK cells in the immune response against Paracoccidioides brasiliensis . (jimmunol.org)
- These results indicate that NK cells participate actively in the immune response against the P. brasiliensis infection either by directly destroying yeast cells or by recognizing and killing infected cells. (jimmunol.org)
- The mouse cytomegalovirus (MCMV) represents a helpful model to study NK cell-driven immune responses. (frontiersin.org)
- Natural killer (NK) cells contribute to the host immune response by recognizing and killing viral-infected and tumor cells ( 1 ). (frontiersin.org)
- We suggest that overexpression of an inhibitory NK receptor might lead to a novel immune deficiency associated with primary CMV infection. (bloodjournal.org)
- In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. (hindawi.com)
- Recent studies focused on development and functional diversity of innate immune cells have led to the reclassification of these cell types into a large group known as innate lymphoid cells (ILCs) [ 1 ]. (hindawi.com)
- As such, NK cells have many roles, in protection, in helping to maintain immune homeostasis, and in long term immunity. (hindawi.com)
- NK cells, among other cells, are key effector cells of the innate immune system and play a crucial role in the antiviral response. (cdc.gov)
- Natural killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. (sciencemag.org)
- NK cells are key players in the innate immune response to pathogens ( 1 ). (rupress.org)
- Natural Killer (NK) cells are important in early innate immune responses to viral infections. (jove.com)
- Natural killer (NK) cells are a vital component of the innate immune response to virus-infected cells. (jove.com)
- Extensive genetic polymorphism is a primary characteristic of the human major histocompatibility complex (MHC) HLA class I and class II loci, which encode products that present antigenic peptides to T cells, initiating an adaptive immune response and clearance of foreign material. (ragoninstitute.org)
- We identified different immune cell subtypes and their heterogeneous transcription factors and depicted their developmental trajectories. (aging-us.com)
- While antibodies that block immune checkpoint proteins, including cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death protein 1 (PD-1), have been approved to treat a variety of cancers [ 2 ], the majority of cancer patients see little benefits from these treatments. (aging-us.com)
- Indeed, the identification of effective therapeutic bio- markers requires an in-depth understanding of tumor-resident immune cells. (aging-us.com)
- In the present study, we analyzed immune cells from a cohort of newly-diagnosed GC patients using flow cytometry and RNA-seq. (aging-us.com)
- Adoptive cellular immunotherapy aims at restoring tumour-cell recognition by the immune system, leading to effective tumour cell killing. (biomedcentral.com)
- A major hurdle to the successful immunotherapy of cancer is represented by the difficulty in generating clinically relevant numbers of immune effector cells with potent in vivo anti-tumour activity, especially in heavily pre-treated patients. (biomedcentral.com)
- The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. (aacrjournals.org)
- The mode of action of these anti-PD-1/PD-L1 mAbs is to inhibit the interaction of PD-1 on immune cells with PD-L1 on tumor cells, thus reducing or eliminating immunosuppressive signals, and leading to enhanced immune cell activation. (aacrjournals.org)
- This has been done to obviate any potential toxicity that may result from ADCC-mediated lysis of subsets of immune cells that express PD-L1. (aacrjournals.org)
- T cell immunity to Zika virus showed a multifunctional response to the antigens Env and NS1 and immune regulatory responses to NS5 and C protein. (bvsalud.org)
- Natural killer (NK) cells have an important role in immune defense against viruses and cancer. (bvsalud.org)
- Dr. Trachtenberg also collaborates on studies of HLA and KIR in stem cell transplantation, a unique environment combining individual donor and recipient immune systems. (chori.org)
- HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. (gopubmed.org)
- As one of the first lymphocyte populations to recover 5 , 6 , NK cells play an important role in immune reconstitution following HSCT. (jcancer.org)
- NK cells both modulate the immune system as well as mediate direct killing of malignant or infected cells. (jcancer.org)
- The purpose of this study was to assess innate and adaptive immune cell phenotypes and function of two groups of CFS/ME patients, bedridden (severe) and mobile (moderate). (edu.au)
- Immunological alterations are present in innate and adaptive immune cells and sometimes, immune deregulation appears worse in CFS/ME patients with more severe symptoms. (edu.au)
- A key mechanism of tumor resistance to immune cells is mediated by expression of peptide-loaded HLA class I molecule (HLA-E) in tumor cells, which suppresses NK cell activity via ligation of the NK inhibitory receptor CD94/NK group 2 member A (NKG2A). (jci.org)
- Thus, NKG2A downregulation evades the HLA-E cancer immune checkpoint and increases the antitumor activity of NK cell infusions. (jci.org)
- Because this strategy is easily adaptable to current protocols for clinical-grade immune cell processing, its clinical testing is feasible and warranted. (jci.org)
- Chronic immune cell dysfunction and activation have been demonstrated in patients with GWI, although the literature is not uniform. (biomedcentral.com)
- We exposed GWI patients and matched controls to an exercise challenge to explore differences in immune cell function measured by classic immune assays and gene expression profiling. (biomedcentral.com)
- Our results do not necessarily elucidate the cause of GWI, but they do reveal a role for immune cell dysfunction in sustaining illness. (biomedcentral.com)
- Generally speaking these represent a mobile innate immune purchase Xarelto system response (IFN\3/4), cytotoxic T\lymphocytic response (HLA\I and tapasin), T helper reactions (HLA\II) and NK cells (KIR), which have already been implicated in the results of HCV disease. (bios-mep.info)
- Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. (biomedcentral.com)
- Natural killer (NK) cells are part of the innate immune system and are considered to be the main virally infected- and tumor cell killing units of this branch of the immune system. (biomedcentral.com)
- It targets and eliminates cancer cells by utilizing the body's immune system and generally results in an enduring anti-tumor response and the effective regression of the cancer, while also preventing metastasis and recurrence [ 1 - 3 ]. (thno.org)
- Peptide-based materials are unique and promising tools for cancer therapeutics and they have a variety of activities, including sensing, drug delivery, cell targeting, fate control, deep tumor tissue penetration, and the generation of immune responses for improved anti-tumor therapeutic outcomes [ 4 - 9 ]. (thno.org)
- Recently, peptides have been designed as versatile cancer vaccines that activate innate and adaptive immune systems by interacting with neutrophils, dendritic cells (DCs), macrophages, natural killer (NK) cells, T cells, B cells, etc [ 15 - 17 ]. (thno.org)
- These two receptor gene families and their roles in the immune response are the topic of this chapter. (asmscience.org)
- In contrast to the promiscuity of most NK receptors, the human CD94-NKG2 family solely recognizes the MHC-Ib molecule, HLA-E ( 17 - 20 ). (rupress.org)
- Furthermore, we show that NK cells released granulysin in cultures after being stimulated by P. brasiliensis , and this molecule is able to kill the yeast cells in a dose-dependent manner. (jimmunol.org)
- Additionally, CD4 + T-cell clones from patients but not those from controls acquired de novo expression of the DAP12 molecule, an adapter chain that transmits CD158j-derived signals. (ahajournals.org)
- Patients with ACS can be distinguished from age-matched healthy controls and patients with stable angina by the increased frequency of a subset of CD4 + T cells that are oligoclonally expanded in the peripheral blood and have lost the expression of the costimulatory molecule CD28. (ahajournals.org)
- CD32 molecule is expressed on B cells, monocytes, granulocytes and platelets. (bios-mep.info)
- In the normal autologous setting, all NK cells have at least one inhibitory receptor that interacts with an autologous HLA class I molecule, thus preventing attack against normal cells. (clicktocurecancer.info)
- They express a plethora of cell surface receptors whose engagement initiate signals that culminate in inhibition or activation of effector functions. (biomedcentral.com)
- To bypass HLA-E inhibition, we developed a way to generate highly functional NK cells lacking NKG2A. (jci.org)
- In the previous study, we PRT062607 HCL inhibition showed that TWIK-1 proteins were indicated and localized primarily in the soma and proximal dendrites of dentate gyrus granule cells (DGGCs) and that TWIK-1-mediated outwardly rectifying K+ currents, contributing to the intrinsic excitability of DGGCs 13. (schwitzbiotech.com)
- Two subsets of NK cells have been identified in humans according to their CD56 expression, which apparently differs in phenotype and function. (jimmunol.org)
- Although other NK-like subsets that share functions with conventional NK cells have been recently described 7 , 8 , for the purpose of this review article, we will focus on conventional NK cells. (jcancer.org)
- The association of distinct effector functions with unique NK cell subsets is thought to be developmentally regulated 9 , 10 , which refers to the 'education' or 'licensing' of NK cells. (jcancer.org)
- Mucosal innate lymphocyte subsets have emerged as an important new factor in CD pathogenesis, but the role of NK cells is poorly understood. (caltech.edu)
- We found a slight trend towards greater expression of KIR2DL2/2DL3/2DS2 (5% versus 28%, P = 0.03) at 14 days in patients who survived longer than 6 months from NK cell infusion (N = 4) when compared to those who died within 6 months of NK cell therapy (N=3). (gopubmed.org)
- Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort ( P =0.030 and 0.038, respectively). (nature.com)
Expression of inhibitory2
- Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. (sciencemag.org)
- This early maturation process is shown to be strictly dependent on the expression of inhibitory KIR by the developing NK cells. (jcancer.org)
- A KIR receptor that has specificity for HLA-C ANTIGENS. (umassmed.edu)
- Responses to Zika virus antigens Env and NS1 were polyfunctional with cells making IFNÎ³, TNFα, IL-4, IL-13, and IL-10. (bvsalud.org)
- Class I antigens are presented on all nucleated cells, where they act as cell surface heterodimers that primarily present peptides derived from the cytosol (viral and self peptides) to circulating CD8+ T cells. (chori.org)
- NK cell education and the effect of HIV infection on iCD4 cell surface expression of MHC-I antigens both influenced NK cell responses to autologous iCD4. (biomedcentral.com)
- Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors. (rupress.org)
- CTLR inhibitory receptors include the CD94/NKG2A and the murine Ly49, which is probably analogous to the human KIR. (wikipedia.org)
- TG-driven CIK cells expressed a constellation of NK activating/inhibitory receptors, such as CD158a and CD158b, NKp46, NKG2D and NKG2A/CD94, released high quantities of IL-12p40 and efficiently lysed K562 target cells. (biomedcentral.com)
- describe a novel approach to efficiently inhibiting surface expression of the inhibitory receptor CD94/NK group 2 member A (NKG2A) through retention of the protein in the endoplasmic reticulum. (jci.org)
- After retroviral transduction in human peripheral blood NK cells, these NKG2A protein expression blockers (PEBLs) abrogated NKG2A expression. (jci.org)
- In immunodeficient mice, NKG2A null NK cells were substantially more powerful than NKG2A + NK cells against HLA-E-expressing tumors. (jci.org)
- Importantly, the CMV developed many mechanisms to avoid attack by NK cells and by cytotoxic T lymphocytes (CTLs), 5 including the down-regulation of HLA-A and -B to avoid CTL attack, while maintaining HLA-C expression to avoid NK attack. (bloodjournal.org)
- They are expressed by a subset of NK cells, and can be detected on the surface of sub-populations of peripheral T lymphocytes, mostly of CD8+ phenotype. (beckman.com)
- Some EBOV infections generate a cytokine storm, which hinders peripheral natural killer cells (NK) and T and B lymphocytes. (cdc.gov)
- RCDII presents with a monoclonal expansion of aberrant CD3 − CD7 + icCD3 + intraepithelial lymphocytes (IELs), constituting over 20% of the IEL population and potentially transforming into an invasive lymphoma (enteropathy-associated T cell lymphoma). (bmj.com)
- Squamous cell carcinoma cell lines expressed varying levels of HLA class I, which correlated inversely with cytolysis by natural killer-enriched polyclonal lymphocytes. (aacrjournals.org)
- In particular, we focused on exhausted CD8 + cells and Tregs and discovered that, as compared to control, the IRF8 transcription factor was downregulated in CD8 + tumour-infiltrating lymphocytes (TILs) from GC tissues, and that GC patients with lower IRF8 levels in blood CD8 + T cells tended to be a at a more advanced disease stage. (aging-us.com)
- NK cells develop in the bone marrow and constitute about 5-10% of total lymphocytes in the peripheral circulation and secondary lymphoidal organs. (jcancer.org)
- The control of proviral load of HTLV-1 depends in part of the lysis of infected cells mediated by cytotoxic CD8⁺T lymphocytes and NK (Natural killer) cells. (bvsalud.org)
- Unlike T and B lymphocytes, which readily respond to a variety of stimuli, NK cells typically do not undergo sustained proliferation. (aacrjournals.org)
- Consistent with the function of an inhibitory KIR, incubation of lymphocytes from Mamu-KIR3DL05 + macaques with target cells expressing Mamu-A1*00201 suppressed the degranulation of tetramer-positive NK cells. (prolekare.cz)
- MHC class I interaction with inhibitory KIR is also critical for NK cell education and development of the NK cell repertoire ( 5 , 6 ). (jimmunol.org)
- The ligand-receptor interaction is dominated by charge complementarity with HLA-C specificity being determined by the residue at position 44, as was first shown in binding experiments ( 19 ). (rupress.org)
- Subjects without acute viral encephalitis showed a higher frequency of interaction between KIR2DL2 and HLAC1. (unipa.it)
- 0.01 after multiple testing correction) were identified for the risk of developing BPD, including pathways of ion channels associated (e.g., gated channel activity, ion transmembrane transporter activity, and ion channel activity) and nervous related biological processes (e.g., nervous system development, cytoskeleton, and neuroactive ligand receptor interaction). (blogspot.com)
Ability of NK cells2
- It is important to understand the ability of NK cells to recognize and lyse HIV-1 infected cells because identifying any aberrancy in NK cell function against HIV-infected cells could potentially lead to therapies that would enhance their cytolytic activity. (jove.com)
- Similarly, HHV-6A/B may contribute to Alzheimer's by utilizing a specific NK cell inhibitory receptor to disrupt the ability of NK cells to clear infected cells. (hhv-6foundation.org)
- On the cell surface, these proteins are bound to protein fragments ( peptides ) that have been exported from within the cell. (wikipedia.org)
- On human NK cells, the killer cell Ig-like receptor (KIR) family of receptors can both inhibit and activate the NK cell response through recognition of HLA class I proteins of the MHC ( 3 , 4 ). (jimmunol.org)
- For example, proteins phosphorylated late after receptor stimulation are expected to represent downstream elements of a pathway whereas rapid phosphorylation is expected in the earlier stages of a pathway, especially at the receptor. (mcponline.org)
- Constitutive phosphorylation throughout a receptor stimulation time course is expected for proteins not involved in the pathway ( 10 ). (mcponline.org)
- Concurrently a third lab identified the proteins as the changing element of the AKT8 retrovirus within a rodent T-cell lymphoma and called it Akt (3). (arcillaresearch.com)
- We manufactured several novel observations in the present research in relation to the reaction of CHT proteins to insulin therapy of neural cells. (wallinside.com)
- We present by TIRF microscopy imaging the dynamic motion of CHT proteins in dwell cells and the results of acute and continual drug therapies on the response of these proteins to K+-mediated depolarization.Very first, we present that differentiated SY5Y-CHT cells react to acute publicity of insulin with enhanced phospho-PKB/Akt levels, but that this is attenuated with long-term publicity of the cells to insulin. (wallinside.com)
- Extensive studies have focused on the development of peptide-based cancer vaccines and delivery systems by mimicking the functional domains of proteins with highly specific immuno-regulatory functions or tumor cells fate controls. (thno.org)
- Many of the peptides used in cancer immunotherapy have been derived from the functional domains of proteins and exert specific activities like receptor binding, stimuli responsiveness, cell penetration, and regulation of cell signaling pathways [ 10 - 14 ]. (thno.org)
- Our findings also suggest an important role of natural killer cells (or other KIR -expressing cells) in the progress of HBV-related HCC development. (hindawi.com)
- Because natural killer cells target virally infected host cells and tumor cells, inhibitory KIR receptors are important in facilitating self-tolerance. (wikipedia.org)
- Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. (hindawi.com)
- Natural killer cells (NK cells) are a first line of defense against invading pathogens and cancer. (hindawi.com)
- Natural Killer cells are amongst the earliest responders to viral infection and mediate protective responses by secreting pro-inflammatory cytokines and by direct cytolysis of infected cells. (biomedcentral.com)
- MS patients with a particular haplotype on natural killer cells are more susceptible to HHV-6A infection. (hhv-6foundation.org)
- Palmer JM, Rajasekaran K, Thakar MS, Malarkannan S. Clinical Relevance of Natural Killer Cells Following Hematopoietic Stem Cell Transplantation. (jcancer.org)
- Clinical studies with peptides have indicated that they are efficient, specific, and safe for delivering therapeutic cargos into cells, while also being easy to synthesize and modify. (thno.org)
- Mamu-A1*00201 tetramers folded with certain SIV peptides, but not others, directly stained primary NK cells and Jurkat cells expressing multiple allotypes of Mamu-KIR3DL05. (prolekare.cz)
- 2 It was suggested that such diversity of NK receptors enables the killing of infected cells by at least a subset of NK cells. (bloodjournal.org)
- Conclusion Our studies indicate that the CD3 − CD7 + icCD3 + population is heterogeneous and reveal the existence of a Lin − subset that is distinct from T, B, NK and lymphoid tissue inducer cells. (bmj.com)
- We also quantified the frequency of bona fide regulatory T cells (Treg), a T-cell subset implicated in the down-regulation of anti-tumor immunity, and tested the in vitro cytotoxic activity of CIK cells against NK-sensitive, chronic myeloid leukaemia K562 cells. (biomedcentral.com)
- Of interest, the frequency of Treg cells was lower at any time-point compared with PBMC cultures nurtured with αCD3 mAb. (biomedcentral.com)
- AD patients also had a lower frequency of KIR3DS1, an activating receptor. (hhv-6foundation.org)
- Discussion: Our findings of a lower frequency of activating receptors in patients with acute encephalitis compared to controls could result in a less efficient response of NK cells. (unipa.it)
- The frequency of KIR/HLA genotypes in HESN and in HIV susceptible subjects enrolled in an HIV primary infection cohort was compared to address whether NK cells also play a role at the level of protection from HIV infection. (biomedcentral.com)
- The mechanism by which PKCθ contributes to the first steps of T cell activation has recently been uncovered. (frontiersin.org)
- For example, NK cell activation has been reported to play a critical role in liver inflammation during chronic HBV infection both in HBV transgenic mice and in HBV-infected patients [ 7 - 9 ]. (hindawi.com)
- An infected cell may have lower MHC expression, altering the binding with inhibitory receptors, disrupting the balance of signals, and allowing for NK cell activation. (frontiersin.org)
- Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. (sciencemag.org)
- Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. (sciencemag.org)
- Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR) and HLA class I ligand interactions. (jove.com)
- For example, single-cell sequencing has revealed a T cell exhaustion signature in some types of cancer and its connection to T cell activation [ 7 - 10 ]. (aging-us.com)
- This leads to NK cell activation of anti-HIV functions. (biomedcentral.com)
- 2012). As a result, in this record, we examined if the early event linked with the account activation of NPC growth was conserved in neonatal SVZ tissues civilizations and additional researched the molecular systems by which Tf can be capable to stimulate cell growth. (capecodmushroom.org)
- These effector functions are mediated through multiple independent activation receptors expressed on NK cells. (jcancer.org)
- Absence of an inhibitory receptor-ligand bond lowers the NK cell activation threshold, whereas an activating receptor-ligand bond stimulates the cell, potentially overcoming this threshold and triggering NK cell activation. (biomedcentral.com)
- One newly discovered NK cell activation pathway associated with resistance to HIV-1 infection involves the presence of an iKIR/HLA mismatch between partners. (biomedcentral.com)
- We have shown that TNFR2 functions as one of the earliest members of the TNFR superfamily and plays a critical role in lowering the threshold for T-cell activation and in providing survival signals during the early phase of the T-cell response 6-8. (alk-inhibitors.com)
- Despite TNFR2′s role in providing crucial signals for initial T-cell activation, we found that it plays a critical role in limiting the duration CHIR-99021 clinical trial of T-cell responses by promoting AICD. (alk-inhibitors.com)
- TASK-3 is also highly indicated in the hippocampal region10 and is inhibited from the activation of neurotensin receptor 1 (NTSR1)16. (schwitzbiotech.com)
- We therefore tested the hypothesis that human NK licensing by KIR2DL2/3 and HLA-C1 induces a broader cytokine program that modifies the threshold of pro-inflammatory T cell activation. (caltech.edu)
- Snake venom serine protease that induces platelet aggregation through activation of protease-activated platelet receptors (PAR1/F2R and PAR4/F2RL3). (mybiosource.com)
- Another important finding is that stimulated NK cells are able to produce proinflammatory cytokines (IFN-γ and TNF-α) supporting their immunomodulatory role in the infection. (jimmunol.org)
- Secretion of the above cytokines and NK-cell method for expanding highly cytotoxic clinical-grade NK cells in vitro cytolytic function were IL-2 dose dependent. (slideshare.net)
- Over the years, improvements in culture conditions, such as the addition of αCD3 (OKT3) monoclonal antibody (mAb) at the initiation of culture and the provision of cytokines at the end of culture, translated into better expansion of LAK cells. (biomedcentral.com)
- These cells are highly proinflammatory releasing large amounts of tissue cytokines which can cause insulin resistance through paracrine mechanisms. (labome.org)
- An immunohistochemical analysis of tissues in the neural parenchyma showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2, cytokines IL-1ß, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1 in ZIKV-positive microcephaly cases than in flavivirus-negative controls. (bvsalud.org)
- Pro-inflammatory cytokines, T-cell ratios, and dysregulated mediators of the stress response (including salivary cortisol) were also altered in GWI cases compared to control subjects. (biomedcentral.com)
- Indeed, their reported proliferative responses to cytokines with or without coculture with other cells have generally been modest and of short duration in most studies ( 10 - 16 ). (aacrjournals.org)
- NK Cell Subgroups, Phenotype, and Functions After Autologous Stem Cell Transplantation. (gopubmed.org)
- CD4 + T cells with a unique phenotype, CD4 + CD28 null , are preferentially recruited into culprit lesions. (ahajournals.org)
- CLPs in the mouse BM differentiate into a pre-NK precursor (pre-NKP) with a phenotype of Lin − CD117 − CD127 + and express some NK cell specific receptors including NKG2D and 2B4 (CD244) and negative for classical NK cell markers NK1.1 and CD49b. (hindawi.com)
- This information was used to identify cells with an RCDII-associated phenotype in duodenal biopsies from non-refractory individuals by multicolour flow cytometry. (bmj.com)
- Cells matching this surface lineage-negative (Lin − ) CD7 + CD127 − CD34 − phenotype expressed a functional interleukin-15 (IL-15) receptor and constituted a significant proportion of IELs in duodenal specimens of patients without CD, particularly children, and were also found in the thymus. (bmj.com)
- Cumulative expression of CD158j and DAP12 endowed cytolytic competence on CD4 + CD28 null T cells, allowing them to kill in the absence of T-cell receptor triggering. (ahajournals.org)
- Several lines of evidence relate the activating NK cell receptor KIR3DS1, in the presence or absence of its putative ligand HLA-Bw4, with slower disease progression as well as resistance to HIV-1 infection. (biomedcentral.com)
- The absence of such an iKIR/HLA bond renders donor-derived allogeneic HIV-1 infected cells vulnerable to NK cell responses during HIV-1 transmission. (biomedcentral.com)
- Natural killer cell cytolysis of target cells and cytokine production is controlled by a balance of inhibitory and activating signals, which are facilitated by NK cell receptors. (wikipedia.org)
- The responsiveness of natural killer (NK) cells is controlled by balancing signals from activating and inhibitory receptors. (frontiersin.org)
- Their activity is controlled by balancing signals from a vast repertoire of activating and inhibiting receptors enabling them to distinguish healthy from unhealthy cells ( 2 ). (frontiersin.org)
- Stud- ies are proposed to assess the mechanisms of GPR120 signaling to decipher precisely how signals from this receptor intersect with the inflammatory pathway. (labome.org)
- Insulin transmits its signals through a cell surface tyrosine kinase receptor which stimulates multiple intracellular signaling events (reviewed in reference 41). (arcillaresearch.com)
- NK cell activity is regulated by the integration of signals from these receptors. (biomedcentral.com)
- The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. (biomedcentral.com)
- That TRAF2 provides pro-survival signals is supported by the observation that T cells expressing a dominant negative form of TRAF2 are much more susceptible to TNF-α-mediated cell death 16. (alk-inhibitors.com)
- Regulation of these effector functions stems from a balance of signaling through activating and inhibitory receptors. (jimmunol.org)
- Furthermore, it is necessary to use autologous primary cells to prevent major histocompatibility complex class I mismatches between the target and effector cell that will result in lysis. (jove.com)
- Thus, it would be beneficial to work with a purified infected cell population in order to standardize the effector to target cell ratios between experiments 3,4 . (jove.com)
- The purified infected primary T-cell blasts can then be used as targets in either a degranulation or cytotoxic assay with purified NK cells as the effector population 5-7 . (jove.com)
- Defining CD4 and CD8 effector functions in protection is important considering that antibody responses appear short-lived and T cell memory is potentially more durable. (bvsalud.org)
- Other research suggests that joint inflammation characteristic of this disorder may result from improper folding of the HLA-B27 protein or the presence of abnormal forms of the protein on the cell surface. (wikipedia.org)
- Consequently, down-regulation of MHC-I expression leads to a reduction in HLA-E expression at the cell surface. (rupress.org)
- Their functions are controlled by multiple inhibitory and activating cell surface receptors ( 2 , 3 ). (rupress.org)
- Cell surface receptors containing an immunoglobin domain. (embl.de)
- The cell suspensions had been either utilized to regenerate a fresh passing of NS, or had been straight made on to an adherent surface area: PF 3716556 a Petri dish or a cup coverslip. (capecodmushroom.org)
- Other cell surface receptors commonly expressed in NK cells fall within three families. (jcancer.org)
- Regulation of natural killer (NK) cytolytic activity is a function of engagement of one or more NK surface receptors that may be activating or inhibitory. (asmscience.org)
Long cytoplasmic tail1
- Besides their ability to release large amounts of interferon (IFN)-γ, CD4 + CD28 null T cells express perforin and granzyme B. 11 On triggering of the T-cell receptor, they lyse target cells, including endothelial cells. (ahajournals.org)
- Cancer patient-derived CIK cells were also expanded after priming with TG, but they expressed lower levels of the NKp46 triggering receptor and NKG2D activating receptor, thus manifesting a reduced ability to lyse K562 cells. (biomedcentral.com)