Antigens: Substances that are recognized by the immune system and induce an immune reaction.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.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.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Antigens, 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.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Antigens, CD38: A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Antigens, CD19: Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.Antigens, CD40: A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Antigens, CD20: Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.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.Antigens, CD44: Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)Antigens, CD7: Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.Antigens, CD14: Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.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.CD4-CD8 Ratio: Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.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)Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.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.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antigens, CD56: The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.Antigens, 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.ADP-ribosyl Cyclase: A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.Antigens, Differentiation, Myelomonocytic: Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.Antigens, CD80: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Antigens, CD53: Tetraspanin proteins found at high levels in cells of the lymphoid-myeloid lineage. CD53 antigens may be involved regulating the differentiation of T-LYMPHOCYTES and the activation of B-LYMPHOCYTES.Antigens, CD24: A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.Antigens, CD13: Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system.Antigens, CD86: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.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.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, Polyomavirus Transforming: Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.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.Antigens, Differentiation, B-Lymphocyte: Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.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.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.NAD+ NucleosidaseAntigens, Fungal: Substances of fungal origin that have antigenic activity.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.H-2 Antigens: The major group of transplantation antigens in the mouse.Sialic Acid Binding Ig-like Lectin 3: A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.Antigens, CD18: Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Antigens, CD30: A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.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.Epitopes: Sites on an antigen that interact with specific antibodies.Antigens, CD9: A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.Antigens, CD15: A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.Antigens, Viral, Tumor: Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, CD43: A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.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.Antigens, CD11: A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.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.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, CD59: Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Antigens, CD57: Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.Antigens, CD70: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.Antigens, CD46: A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.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.Antigens, CD58: Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.Antigens, 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.Antigens, CD47: A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.Antigens, CD11b: A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Prostate-Specific Antigen: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.Antigens, CD11c: An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)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.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.CD4 Lymphocyte Count: The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Cell SeparationAntigens, Tumor-Associated, Carbohydrate: Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.Antigens, CD55: GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.Antigens, CD31: Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.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, CD81: Tetraspanin proteins that are involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antigens, CD137: A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Mice, Inbred BALB CMonocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.HLA-A Antigens: Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).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.Blood Group Antigens: Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.Hepatitis B Surface Antigens: Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.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.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antigens, CD151: Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.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.Meningitis, Aseptic: A syndrome characterized by headache, neck stiffness, low grade fever, and CSF lymphocytic pleocytosis in the absence of an acute bacterial pathogen. Viral meningitis is the most frequent cause although MYCOPLASMA INFECTIONS; RICKETTSIA INFECTIONS; diagnostic or therapeutic procedures; NEOPLASTIC PROCESSES; septic perimeningeal foci; and other conditions may result in this syndrome. (From Adams et al., Principles of Neurology, 6th ed, p745)Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.HLA-D Antigens: Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.CD30 Ligand: A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.N-Glycosyl Hydrolases: A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.Burkitt Lymphoma: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.Fermium: Fermium. A man-made radioactive actinide with atomic symbol Fm, atomic number 100, and atomic weight 257. Its known isotopes range from 244-254 and 256-258. Its valence can be +2 or +3. Like einsteinium, it was discovered in 1952 in the debris from a thermonuclear explosion.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antigens, CD11a: An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.RNA, 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.Hepatitis B Antigens: Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Herpesvirus 4, Human: The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.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.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.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.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.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.MART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.Antigens, CD147: A widely distributed cell surface transmembrane glycoprotein that stimulates the synthesis of MATRIX METALLOPROTEINASES. It is found at high levels on the surface of malignant NEOPLASMS and may play a role as a mediator of malignant cell behavior.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Mice, Inbred C57BLOvalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.HIV Antigens: Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.CTLA-4 Antigen: An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Antigens, CD82: A widely expressed transmembrane glycoprotein that functions as a METASTASIS suppressor protein. It is underexpressed in a variety of human NEOPLASMS.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Antigens, Thy-1: A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.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.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.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.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.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.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)Epstein-Barr Virus Nuclear Antigens: Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.H-Y Antigen: A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.Antigens, CD146: A cell adhesion molecule of the immunoglobulin superfamily that is expressed in ENDOTHELIAL CELLS and is involved in INTERCELLULAR JUNCTIONS.Antigens, Heterophile: Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Epitopes, 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.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.Antigens, CD98: A heterodimeric protein that is a cell surface antigen associated with lymphocyte activation. The initial characterization of this protein revealed one identifiable heavy chain (ANTIGENS, CD98 HEAVY CHAIN) and an indeterminate smaller light chain. It is now known that a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS) can dimerize with the heavy chain. Depending upon its light chain composition a diverse array of functions can be found for this protein. Functions include: type L amino acid transport, type y+L amino acid transport and regulation of cellular fusion.Hepatitis B Core Antigens: The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.Benzocaine: A surface anesthetic that acts by preventing transmission of impulses along NERVE FIBERS and at NERVE ENDINGS.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.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.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.Forssman Antigen: A glycolipid, cross-species antigen that induces production of antisheep hemolysin. It is present on the tissue cells of many species but absent in humans. It is found in many infectious agents.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Antigens, CD274: An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.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.gp100 Melanoma Antigen: A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.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.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.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.

Biochemical characterization of CD1d expression in the absence of beta2-microglobulin. (1/609)

CD1d is a major histocompatibility complex class I-like molecule that exhibits a distinct antigen processing pathway that functions in the presentation of hydrophobic antigens to T cells. CD1d has been previously shown to be expressed on the cell surface of human intestinal epithelial cell lines in vivo and a transfected cell line in vitro independently of beta2-microglobulin (beta2m). To define the relationship between CD1d and beta2m and characterize the biochemical structure of CD1d in the absence of beta2m, we have used a newly generated series of CD1d transfectants and CD1d-specific antibodies. These studies show that in the absence of beta2m, CD1d is expressed on the cell surface as a 45-kDa glycoprotein that is sensitive to endoglycosidase-H and is reduced to 37-kDa after N-glycanase digestion. In contrast, in the presence of beta2m, CD1d is expressed on the cell surface as a 48-kDa endoglycosidase-H-resistant glycoprotein. Pulse-chase metabolic labeling studies demonstrate that acquisition of endoglycosidase-H resistance of CD1d is observed in the presence of beta2m but not in the absence of beta2m even after a 24-h chase period. Thus, CD1d is able to be transported to the cell surface independently of beta2m; however, in the absence of beta2m, the glycosylation pattern of CD1d is altered and consistent with an immature glycoprotein.  (+info)

Juvenile hemochromatosis locus maps to chromosome 1q. (2/609)

Juvenile hemochromatosis (JH) is an autosomal recessive disorder that leads to severe iron loading in the 2d to 3d decade of life. Affected members in families with JH do not show linkage to chromosome 6p and do not have mutations in the HFE gene that lead to the common hereditary hemochromatosis. In this study we performed a genomewide search to map the JH locus in nine families: six consanguineous and three with multiple affected patients. This strategy allowed us to identify the JH locus on the long arm of chromosome 1. A maximum LOD score of 5.75 at a recombination fraction of 0 was detected with marker D1S498, and a LOD score of 5. 16 at a recombination fraction of 0 was detected for marker D1S2344. Homozygosity mapping in consanguineous families defined the limits of the candidate region in an approximately 4-cM interval between markers D1S442 and D1S2347. Analysis of genes mapped in this interval excluded obvious candidates. The JH locus does not correspond to the chromosomal localization of any known gene involved in iron metabolism. These findings provide a means to recognize, at an early age, patients in affected families. They also provide a starting point for the identification of the affected gene by positional cloning.  (+info)

Immunolocalization of CD1d in human intestinal epithelial cells and identification of a beta2-microglobulin-associated form. (3/609)

In order to better understand the role of intestinal CD1d, we sought to define the cellular localization and further characterize the biochemical structure of CD1d in human intestinal epithelial cells (IEC). Using a CD1d-specific rabbit anti-gst-CD1d antibody, immunoprecipitation of radiolabeled cell surface proteins detected a previously identified 37 kDa protein as well as a 48-50 kDa protein which were confirmed by Western blotting with a CD1d-specific mAb, D5. Immunoprecipitation of protein lysates with the CD1d-specific mAb, D5 and 51.1.3, and the beta2-microglobulin (beta2m)-specific mAb, BBM.1, followed by N-glycanase digestion and Western blotting with the D5 mAb showed that the 48-50 kDa protein was a beta2m-associated, CD1d glycoprotein. CD1d was immunolocalized to the apical and lateral regions of native small and large intestinal IEC as defined by confocal laser microscopy using the D5 mAb and the rabbit anti-gst-CD1d antibody. In addition, a large apical intracellular pool of CD1d was identified. Identical observations were made with polarized T84 cells. Selective biotin labeling of apical and basolateral cell surfaces followed by immunoprecipitation with the D5 mAb, N-glycanase digestion and avidin blotting confirmed the presence of glycosylated CD1d on both cell surfaces and immunolocalization of the 37 kDa non-glycosylated form of CD1d to the apical cell surface. These studies show that CD1d is located in an ideal position for luminal antigen sampling and presentation to subjacent intraepithelial lymphocytes.  (+info)

Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells. (4/609)

NKT cells, defined as T cells expressing the NK cell marker NK1.1, are involved in tumor rejection and regulation of autoimmunity via the production of cytokines. We show in this study that two types of NKT cells can be defined on the basis of their reactivity to the monomorphic MHC class I-like molecule CD1d. One type of NKT cell is positively selected by CD1d and expresses a biased TCR repertoire together with a phenotype found on activated T cells. A second type of NKT cell, in contrast, develops in the absence of CD1d, and expresses a diverse TCR repertoire and a phenotype found on naive T cells and NK cells. Importantly, the two types of NKT cells segregate in distinct tissues. Whereas thymus and liver contain primarily CD1d-dependent NKT cells, spleen and bone marrow are enriched in CD1d-independent NKT cells. Collectively, our data suggest that recognition of tissue-specific ligands by the TCR controls localization and activation of NKT cells.  (+info)

A novel recognition motif of human NKT antigen receptor for a glycolipid ligand. (5/609)

Murine NKT cells can recognize alpha-galactosylceramide (alpha-GalCer) in the context of a class Ib CD1d molecule. Here we show that alpha-GalCer can selectively activate freshly isolated human Valpha24(+)Vbeta11(+) cells, functionally defining the human NKT cells. The naive human NKT cell repertoire consisted of cells expressing an invariant Valpha24JalphaQ chain and a diverse array of beta chains derived from a single Vbeta11 gene segment. Stimulation with alpha-GalCer expanded a polyclonal subset of the human NKT cell repertoire carrying a novel complementarity-determining region (CDR) 3beta consensus motif that may directly interact with the sugar moiety of alpha-GalCer. Our data suggest that certain redundancy is allowed for CDR3beta of NKT antigen receptor to interact with the ligand and provide a first clue to understand the novel protein-carbohydrate interaction mechanisms.  (+info)

Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis. (6/609)

Cellular immunity against Mycobacterium tuberculosis controls infection in the majority of infected humans. Studies in mice have delineated an important role for CD4(+) T cells and cytokines including interferon gamma and tumor necrosis factor alpha in the response to infection with mycobacteria. Recently, the identification of CD8(+) CD1-restricted T cells that kill M. tuberculosis organisms via granulysin and the rapid death after infection of beta2 microglobulin deficient mice in humans has drawn attention to a critical role for CD8(+) T cells. The nature of mycobacterial-specific CD8(+) T cells has been an enigma because few have been identified in any species. Here, we delineate the contribution of class I MHC-restricted T cells in the defense against tuberculosis as transporter associated with antigen processing (TAP)1-deficient mice died rapidly, bore a greater bacterial burden, and had more severe tissue pathology than control mice. In contrast, CD1D-/- mice were not significantly different in their susceptibility to infection than control mice. This data demonstrates a critical role for TAP-dependent peptide antigen presentation and provides further evidence that class I MHC-restricted CD8(+) T cells, the major T cell subset activated by this antigen processing pathway, play an essential role in immunity to tuberculosis.  (+info)

Cutting edge: activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. (7/609)

NK T cells recognize glycolipid Ags such as alpha-galactosylceramide (alpha-GalCer) presented by the MHC class I-like molecule CD1d. In this paper we have studied the in vivo effects of alpha-GalCer on the generation of adaptive immune responses. Treatment of mice with alpha-GalCer resulted in rapid activation of NK T cells and production of the cytokines IL-4 and IFN-gamma. However, after this initial stimulation, NK T cells became polarized for the production of IL-4. Further, as soon as 6 days after alpha-GalCer injection, a marked increase in serum IgE levels was observed. Administration of alpha-GalCer at the time of priming of mice with protein Ag resulted in the generation of Ag-specific Th2 cells and a profound increase in the production of IgE. Collectively, these findings indicate that alpha-GalCer may be useful for modulating immune responses toward a Th2 phenotype during prophylaxis and therapy.  (+info)

Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone. (8/609)

NK T cells are a T cell subset in the human that express an invariant alpha-chain (V alpha 24invt T cells). Because of the well-described immunomodulation by glucocorticoids on activation-induced cell death (AICD), the effects of dexamethasone and anti-CD3 stimulation on V alpha 24invt T cell clones and CD4+ T cell clones were investigated. Dexamethasone significantly enhanced anti-CD3-mediated proliferation of V alpha 24invt T cells, whereas CD4+ T cells were inhibited. Addition of neutralizing IL-2 Ab partially abrogated dexamethasone-induced potentiation of V alpha 24invt T cell proliferation, indicating a role for autocrine IL-2 production in corticosteroid-mediated proliferative augmentation. Dexamethasone treatment of anti-CD3-stimulated V alpha 24invt T cells did not synergize with anti-Fas blockade in enhancing proliferation or preventing AICD. The V alpha 24invt T cell response to dexamethasone was dependent on the TCR signal strength. In the presence of dexamethasone, lower doses of anti-CD3 inhibited proliferation of V alpha 24invt T cells and CD4+ T cells; at higher doses of anti-CD3, which caused inhibition of CD4+ T cells, the V alpha 24invt T cell clones proliferated and were rescued from AICD. These results demonstrate significant differences in TCR signal strength required between V alpha 24invt T cells and CD4+ cells, and suggest important immunomodulatory consequences for endogenous and exogenous corticosteroids in immune responses.  (+info)

*Immudex

Cancer Testis Antigen CD1d Dextramer - These MHC Dextramers are flow cytometry reagents for the identification and sorting of ... The CD1d/α-GalCer displays human CD1d molecules loaded with α-GalCer. Though Immudex specializes in MHC Dextramer technology, ... The use of MHC Dextramers offers a new method to accurately detect and quantify antigen-specific CD8+ T cells. While some of ... The process of negative selection in the thymus guarantees that virtually all T cells have very weak affinity for self-antigens ...

*CD1D

... is the only member of the group 2 CD1 molecules. CD1d-presented lipid antigens activate a special class of T cells, known ... CD1d antigen at the US National Library of Medicine Medical Subject Headings (MeSH) Human CD1A genome location and CD1A gene ... CD1d is also known as R3G1 Some of the known ligands for CD1d are: α-galactosylceramide (α-GalCer), a compound originally ... CD1D is the human gene that encodes the protein CD1d, a member of the CD1 (cluster of differentiation 1) family of ...

*Natural killer T cell

iNKT cells recognize lipid antigens presented by CD1d, a non-polymorphic major histocompatibility complex class I-like antigen ... Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and foreign ... recognize lipids and glycolipids presented by CD1d molecules, a member of the CD1 family of antigen-presenting molecules, ... which is specific for glycolipid antigens. The best known antigen of iNKT cells is α-galactosylceramide(αGalCer), which is a ...

*CD1

... a, CD1b and CD1c (group 1 CD1 molecules) are expressed on cells specialized for antigen presentation. CD1d (group 2 CD1) is ... CD1 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) Mouse CD Antigen Chart Human CD Antigen ... Natural Killer T (NKT) cells are activated by CD1d-presented antigens, and rapidly produce Th1 and Th2 cytokines, typically ... Thus, mice have been used extensively to characterize the role of CD1d and CD1d-dependent NKT cells in a variety of disease ...

*Isoglobotriosylceramide

It has been identified as a CD1d- presented self-antigen for an innate type of immune cells termed as Natural Killer T (NKT) ...

*Sulfatide

CD1a, CD1b, and CD1c subtypes present lipid antigens to T cells, while CD1d cells present lipids, glycolipids, and lipoproteins ... However, when CD1d deficient-mice are tested for their response to sulfatide, the same response is not seen, which indicates ... There are two types of cell subtypes that interact with CD1d cells: Type 1 Natural killer T cells and Type 2 Natural killer T ... Type 2 Natural killer T cells are able to recognize sulfatide/ CD1d tetramers, and as a result, they are activated by different ...

*T cell

NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ... Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... These self-antigens are expressed by thymic cortical epithelial cells on MHC molecules on the surface of cortical epithelial ... The second signal licenses the T cell to respond to an antigen. Without it, the T cell becomes anergic, and it becomes more ...

*Vitellogenin lipid transport domain

CD1d being the MHC I-like lipid antigen presenting molecule. Apolipoprotein B can exist in two forms: B-100 and B-48. ... "A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d". J. Exp. Med. 204 (4 ... MTTP is also involved in the late stage of CD1d trafficking in the lysosomal compartment, ...

*MHC multimer

2001). "Antigen-specific modulation of an immune response by in vivo administration of soluble MHC class I tetramers". J. ... Multimers may be used to display class 1 MHC, class 2 MHC, or nonclassical molecules (e.g. CD1d) from species such as monkeys, ... MHC pentamers have been used in the detection of antigen-specific CD8+ T cells in flow cytometry, and are cited in over 750 ... MHC multimers allow for ex vivo selection and proliferation of T-cells specific to viral or tumor-related antigens, which can ...

*Innate immune system

Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens ... Like other 'unconventional' T cell subsets bearing invariant T cell receptors (TCRs), such as CD1d-restricted Natural Killer T ... Dendritic cells are very important in the process of antigen presentation, and serve as a link between the innate and adaptive ... causing the death of the pathogen rid the body of neutralised antigen-antibody complexes. There are three different complements ...

*Gamma delta T cell

The antigens recognized by non-Vδ2 T cells expanded in the above infectious contexts have not been characterized, but the fact ... Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted Natural Killer T cells, gamma delta ... It is still not clear whether these non-peptidic antigens bind directly to the Vγ9/Vδ2 TCR or if a presenting element exists. ... However, none of the known antigen-presenting molecules like MHC class I and II or CD1 are required for γδ T cell activation ...

*Betty Diamond

XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development J ... Expansion and hyperactivity of CD1d-restricted NKT cells during the progression of systemic lupus erythematosus in New Zealand ... 109:1625-1633 (2002). Newman, J., Rice, JS., Wang, C., Harris, SL., and Diamond, B. Identification of an antigen-specific B ... 111:275-283 (2003). Wang, C., Khalil, M., Ravetch, J., and Diamond, B. The naïve B cell repertoire predisposes to antigen- ...

*Adaptive immune system

Exogenous antigens are usually displayed on MHC class II molecules, which activate CD4+T helper cells. Endogenous antigens are ... Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted natural killer T cells, γδ T cells ... A critical difference between B cells and T cells is how each cell "sees" an antigen. T cells recognize their cognate antigen ... The host's cells express "self" antigens. These antigens are different from those on the surface of bacteria or on the surface ...

*Immune system

... antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are ... Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted Natural Killer T cells, γδ T cells ... Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to ... Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex ...

*HLA-G

... histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is ... Sköld M, Behar SM (2003). "Role of CD1d-Restricted NKT Cells in Microbial Immunity". Infect. Immun. 71 (10): 5447-55. doi: ... McIntire RH, Hunt JS (2005). "Antigen presenting cells and HLA-G--a review". Placenta. 26 Suppl A: S104-9. doi:10.1016/j. ... Moreau P, Dausset J, Carosella ED, Rouas-Freiss N (2003). "Viewpoint on the functionality of the human leukocyte antigen-G null ...

*Immunoglobulin C1-set domain

AZGP1; B2M; CD1A; CD1B; CD1C; CD1D; CD1E; DMA; DQB2; DRB1; ELK2P1; FCGRT; HFE; HHLA2; HLA-A; HLA-B; HLA-B35; HLA-B57; HLA-C; ... Cresswell P, Pamer E (1998). "Mechanisms of MHC class I--restricted antigen processing". Annu. Rev. Immunol. 16 (1): 323-358. ...

*Calreticulin

... but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen, but this was later ... Zhu Y, Zhang W, Veerapen N, Besra G, Cresswell P (Dec 2010). "Calreticulin controls the rate of assembly of CD1d molecules in ... This association prepares the MHC class I for binding an antigen for presentation on the cell surface. Calreticulin is also ... "A human Ro/SS-A autoantigen is the homologue of calreticulin and is highly homologous with onchocercal RAL-1 antigen and an ...

*Regulatory B cells

Mouse Bregs were mainly CD5 and CD1d positive in model of EAE or after exposition of Leishmania major. By contrast mouse Bregs ... "IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses". The ...
Age-related immune dysfunction presents serious health concerns for todays society, as the population of individuals over the age of 65 years old continues to expand. The consequences of immunosenescence are obvious, as aged individuals are less able to ward off bacterial, viral, and fungal infections, have higher incidences of cancer, and have overall decreased responses to protective vaccines compared with younger individuals (4, 14). Age-related changes in adaptive immunity are well documented, whereas less is known about the effects of age on the innate immune system, with particular regard to innate lymphocytes such as CD1d-restricted NKT cells. Here, we show that as age advances, the number of CD1d-restricted NKT cells increases and that these cells in the aged immune microenvironment actively suppress, rather than support efferent T cell immunity. Additionally, our findings support the concept that NKT cells may suppress efferent T cell immunity via mechanisms that involve excess ...
CD1d-restricted natural killer T (NKT) cells can have multiple effects on an immune response, including the activation, regulation and attraction of innate immune cells, and modulation of adaptive immunity. Recent studies reveal that there are distinct subsets of NKT cells which selectively perform some of the functions attributed to CD1d-restricted cells, but the mechanisms underlying these functional differences have not been resolved. Our aim in this study was to identify novel NKT cell associated traits that would provide important insight into NKT cell activation and function. To this end, we have performed gene expression profiling of two separate subsets of NKT cells, analyzing genes differentially expressed in these cells compared to conventional CD4(+)NK1.1(-) T cells. We identify different sets of genes over expressed in each of the two NKT cell types, as well as genes that are common to the two CD1d-restricted NKT cell populations analyzed. A large number of these genes are highly ...
NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two
To the Editor: Interleukins (IL) are potent biomolecules used for immunotherapy in cancer and infectious diseases. The clinical benefit of cytokines is linked to their strong effects on immune cells, and these effects are important to study in patients undergoing treatment because the cellular responses in vivo may differ from those seen in vitro. We therefore read with interest the study by van der Vliet et al. (1) concerning the effect of high-dose IL-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancer. The main conclusion presented by the authors is that CD25+ regulatory T cells, which have an inhibitory effect on adaptive T-cell responses, increased during therapy. Conversely, the CD1d-restricted natural killer T (NKT) cells, which have mainly activating effects on other immune cells, decreased in numbers during therapy. One might speculate that such effects of IL-2 could suppress some cellular immune responses against the tumor and thus be detrimental ...
It has been suggested that NKT cells are biased toward CD1d autoreactivity. Consistent with this, NKT cells have an activated/effector or memory phenotype, even in germ free animals (58). Also, some NKT cell hybridomas exhibit CD1d autoreactivity (59), and freshly isolated NKT cells respond to CD1d transfectants and DCs (60). In light of this possible autoreactivity, it remained to be shown whether NKT cell precursors that encounter a strong signal during development undergo negative selection, and if so, what cell type(s) can mediate the negative selection of NKT cells. In this study, we showed that the addition of an agonist glycolipid into FTOC or increasing CD1d surface expression by transgenesis resulted in a drastic reduction of NKT cells, supporting the notion that NKT cells are susceptible to negative selection. This is the first demonstration that a glycolipid can induce negative selection of a T cell population. Although our models do not directly address whether NKT cells can be ...
Fast delivery of PPP1R3D knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
Fast delivery of EIF2D knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
Vicodin, Symtan, Anexsia, Dicodid, Hycodan (or generically Hydromet), Hycomine, Hycet, Lorcet, Lortab, Norco, Novahistex, Hydrovo, Duodin, Kolikodol, Orthoxycol, Mercodinone, Synkonin, Norgan, Hydrokon ...
NKT cells are a unique population of T cells that recognize lipid antigens presented by a nonclassical MHC-like molecule CD1d. There are two types of NKT cells, type I and type II. Our group previously showed that type I NKT cells enhance and type II NKT cells suppress anti-tumor responses, and that these two types of NKT cells cross-regulate each other. One of the defined antigens for type I NKT cells is alpha-galactosylceramide (aGC), and aGC-loaded CD1d tetramers are widely used to study them. Unlike conventional T cells, each subset of NKT cells recognizes distinct antigens. Sulfatide (3-o-sulfo-beta-D-galactosylceramide), an endogenous lipid, is the only lipid proven to be recognized by type II NKT cells in vivo. In addition, recently phosphatidylglycerol (PG) and phosphatidylinositol (PI), also endogenous lipids, were reported to be recognized by type II NKT cell hybridomas. So far, type II NKT cells and their antigens are much less well characterized than type I due to lack of widely ...
TY - JOUR. T1 - Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. AU - King, Irah L.. AU - Fortier, Anne. AU - Tighe, Michael. AU - Dibble, John. AU - Watts, Gerald F.M.. AU - Veerapen, Natacha. AU - Haberman, Ann M.. AU - Besra, Gurdyal S.. AU - Mohrs, Markus. AU - Brenner, Michael B.. AU - Leadbetter, Elizabeth A.. PY - 2012/1/1. Y1 - 2012/1/1. N2 - Mouse invariant natural killer T cells (iNKT cells) provide cognate and noncognate help for lipid and protein-specific B cells, respectively. However, the long-term outcome for B cells after cognate help is provided by iNKT cells is unknown at present. Here we found that cognate iNKT cell help resulted in a B cell differentiation program characterized by extrafollicular plasmablasts, germinal-center formation, affinity maturation and a robust primary immunoglobulin G (IgG) antibody response that was uniquely dependent on iNKT cell-derived interleukin 21 (IL-21). However, cognate help ...
TY - JOUR. T1 - Invariant Natural Killer T Cells Suppress the Neutrophil Inflammatory Response in a Mouse Model of Cholestatic Liver Damage. AU - Wintermeyer, Philip. AU - Cheng, Chao Wen. AU - Gehring, Stephan. AU - Hoffman, Beth L.. AU - Holub, Martin. AU - Brossay, Laurent. AU - Gregory, Stephen H.. PY - 2009/3. Y1 - 2009/3. N2 - Background & Aims: NK1.1+ TCRαβint CD1-restricted T (NKT) cells are a unique subset of T lymphocytes that are believed to have an immunoregulatory role in a wide range of diseases. Most mouse NKT cells express a T-cell receptor that contains an invariant Vα14Jα18 chain and recognizes antigenic glycolipids presented in association with major histocompatibility complex class Ib (CD1d) molecules. These invariant NKT (iNKT) cells have been implicated in cholestatic liver injury. Methods: We examined the role of iNKT cells in liver injury associated with biliary obstruction in mice with ligations of the common bile duct. Results: The number of activated iNKT cells ...
CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokine-biasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can ...
Objective: Inflammatory mediators play a crucial role in the development of chronic heart failure (HF). Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes, which recognize glycolipid antigens and secrete a large amount of T helper (Th) 1/Th2 cytokines on activation, function as immunomodulatory cells in the various pathological processes. We have demonstrated that iNKT cells have a protective role against the development of left ventricular (LV) remodeling and failure after myocardial infarction in mice. However, it remains unclear whether iNKT cells are involved in the development of HF in humans.. Methods and Results: Nine HF patients (NYHA II or III, LV ejection fraction 26.3±3.0%) and 8 healthy controls were studied. The mean age and male gender were comparable between HF and controls (51.2±5.1 vs. 45.1±4.5 years and 77.8 vs. 75.0%). The causes of HF were idiopathic dilated cardiomyopathy in 3, ischemic in 2, and others in 4 patients. Plasma BNP was significantly ...
Invariant natural killer T (iNKT) cells represent a unique population of CD1d-restricted T lymphocytes expressing an invariant T cell receptor (TCR) encoded by Vα14-Jα18 and Vα24-Jα18 gene segments in mice and humans, respectively. Recognition of CD1d-loaded endogenous lipid antigen(s) on CD4/CD8-double positive (DP) thymocytes is essential for the development of iNKT cells. The lipid repertoire of DP thymocytes and the identity of the decisive endogenous lipid ligands have not yet been fully elucidated. Glycosphingolipids (GSL) were implicated to serve as endogenous ligands. However, further in vivo investigations were hampered by early embryonal lethality of mice deficient for the key GSL-synthesizing enzyme glucosylceramide (GlcCer) synthase (GCS, EC 2.4.1.80). We have now analyzed the GSL composition of DP thymocytes and shown that GlcCer represented the sole neutral GSL and the acidic fraction was composed of gangliosides. Furthermore, we report on a mouse model that by combination of Vav
Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis. . Download books free in pdf. Online library with books, university works and thousands of documents available to read online and download.
Background Natural killer T (NKT) cells are a subset of T cells that help potentiate and regulate immune responses. Although human NKT cell subsets with distinct effector functions have been identified, it is unclear whether the effector functions of these subsets are imprinted during development or can be selectively reprogrammed in the periphery. Results We found that neonatal NKT cells are predominantly CD4+ and express higher levels of CCR7 and CD62L and lower levels of CD94 and CD161 than adult CD4+ or CD4− NKT cell subsets. Accordingly, neonatal NKT cells were more flexible than adult CD4+ NKT cells in their capacity to acquire Th1- or Th2-like functions upon either cytokine-mediated polarization or ectopic expression of the Th1 or Th2 transcription factors T-bet and GATA-3, respectively. Consistent with their more differentiated phenotype, CD4- NKT cells were predominantly resistant to functional reprogramming and displayed higher cytotoxic function. In contrast to conventional T cells,
Background Natural killer T (NKT) cells are a subset of T cells that help potentiate and regulate immune responses. Although human NKT cell subsets with distinct effector functions have been identified, it is unclear whether the effector functions of these subsets are imprinted during development or can be selectively reprogrammed in the periphery. Results We found that neonatal NKT cells are predominantly CD4+ and express higher levels of CCR7 and CD62L and lower levels of CD94 and CD161 than adult CD4+ or CD4− NKT cell subsets. Accordingly, neonatal NKT cells were more flexible than adult CD4+ NKT cells in their capacity to acquire Th1- or Th2-like functions upon either cytokine-mediated polarization or ectopic expression of the Th1 or Th2 transcription factors T-bet and GATA-3, respectively. Consistent with their more differentiated phenotype, CD4- NKT cells were predominantly resistant to functional reprogramming and displayed higher cytotoxic function. In contrast to conventional T cells,
Mice deficient in p53 are predisposed to develop cancer, such as TL and sarcoma, with 100% cancer-related mortality by ∼300 d (Donehower et al., 1992; Jacks et al., 1994). However, little is known about the role of p53 in mature T cell lymphomagenesis, although structural rearrangements of at least 1 of 5 p53-related genes have been described in 67% of PTCLs (Vasmatzis et al., 2012). In this study, using p53−/− mice, we identified a new entity of PTCL that does not originate from conventional T cells but from CD1d-restricted T cells. Most PTCLs arising in p53−/− mice were derived from iNKT cells, the most abundant CD1d-restricted T cell subset in mice. The iNKT origin of these PTCLs was demonstrated by CD1d-αGalCer tetramer staining, expression of the transcription factor PLZF or ZBTB16, invariant Vα14-Jα18 rearrangement of the TCR Vα chain, and rapid secretion of Th1 and Th17 cytokines upon activation. Although these lymphomas have never been characterized in previous studies, ...
NKT cells represent a unique subset of immunoregulatory T cells that recognize glycolipid Ags presented by the MHC class I-like molecule CD1d. Because of their immunoregulatory properties, NKT cells are attractive targets for the development of immunotherapies. The prototypical NKT cell ligand alpha-galactosylceramide (alpha-GalCer), originally isolated from a marine sponge, has potent immunomodulatory activities in mice, demonstrating therapeutic efficacy against metastatic tumors, infections, and autoimmune diseases, but also has a number of adverse side effects. In vivo administration of alpha-GalCer to mice results in the rapid activation of NKT cells, which is characterized by cytokine secretion, surface receptor down-regulation, expansion, and secondary activation of a variety of innate and adaptive immune system cells. In this study, we have evaluated the in vivo immune response of mice to a set of structural analogues of alpha-GalCer. Our results show that, contrary to current thinking, beta
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Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, September ...
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Hereditary lupus of NZB/W mice is an Ab-mediated systemic autoimmune disease in which the Th1 cytokine IFN-γ has been shown to play an important role in the pathogenesis of tissue injury (57). Anti-IFN-γ mAb treatment has been reported to ameliorate the immune complex glomerulonephritis, the hallmark of the disease (21). In addition, introduction of a transgene encoding the Th2 cytokine IL-4 into lupus-prone (NZW × C57BL/6.Yaa) F1 mice prevented lupus development (58). We have recently reported that adoptive transfer of CD1d-reactive transgenic CD4 T cells with a Th1-like cytokine-secretion pattern induced lupus in BALB/c nu/nu recipients (8). CD1d-reactive T cells have also been suggested to play a role in augmenting IgG2a anti-dsDNA secretion and lupus development in lupus-prone NZB/W mice (20). It is not yet clear, however, whether activation of the CD1d-reactive T cells in NZB/W mice contributed to the IFN-γ secretion that shifted the autoantibody secretion toward the pathogenic IgG2a ...
Invariant NKT (iNKT) cells can prevent diabetes by inhibiting the differentiation of anti-islet T cells. We recently showed that neither iNKT cell protection against diabetes nor iNKT cell inhibition of T cell differentiation in vitro requires cytokines such as IL-4, IL-10, IL-13, and TGF-beta. In contrast, cell-cell contacts were required for iNKT cell inhibition of T cell differentiation in vitro. The present study was designed to determine whether the CD1d molecule is involved in the inhibitory function of iNKT cells. Experiments were performed in vitro and in vivo, using cells lacking CD1d expression. The in vivo experiments used CD1d-deficient mice that were either reconstituted with iNKT cells or expressed a CD1d transgene exclusively in the thymus. Both mouse models had functional iNKT cells in the periphery, even though CD1d was not expressed in peripheral tissues. Surprisingly, both in vitro inhibition of T cell differentiation by iNKT cells and mouse protection against diabetes by iNKT cells
Abstract: CD1d-restricted T-cells are activated by glycolipids presented by the major histocompatibility complex class-Ib molecule CD1d, found on the surface of antigen-presenting cells (APC). This interaction between APC, most notably dendritic cells (DC), and CD1d-restricted T-cells is an important regulatory step in the initiation of adaptive immune responses. It is well known that DC play a crucial role in the induction of contact hypersensitivity (CHS), a frequently studied form of in vivo T-cell-mediated immunity. In this study, we show that CD1d-restricted T-cells are also necessary for CHS, because both wild-type mice treated systemically or topically with CD1d glycolipid antagonists and CD1d-restricted T-cell-null mice have markedly diminished CHS responses. Thus, pharmacologic antagonists of CD1d can be used as effective inhibitors of CHS, a prototype for a variety of delayed-type tissue hypersensitivity responses. ...
Data presented in this paper provide the first example of how negative regulation of NKT cell signalling contributes to NKT cell development. In contrast to the known NKT regulators, CYLD is dispensable for NKT cell maturation. In fact, the CYLD KO mice contain a substantially higher frequency of NK1.1+ mature NKT cells. This phenotype is associated with a hyper‐activation phenotype, particularly in the immature NKT populations. However, although loss of CYLD seems to accelerate the process of NKT cell maturation, the CYLD KO mice display a severe reduction in the number of NKT cells in both the thymus and the periphery. This deficiency is due to the massive apoptosis of immature NKT cells. Thus, in contrast to its pro‐apoptotic function implicated in other cell types, particularly tumour cells (Sun, 2010), CYLD has a potent anti‐apoptotic function in immature NKT cells, which is crucial for NKT cell development.. The hyper‐activated phenotype of CYLD KO NKT cells indicated the ...
The highly conserved CD1d-restricted NKT cells, identified as a bridge between innate and adaptive immune responses, exert potent immune regulatory functions by releasing a variety immunomodulatory cytokines. Up to now, the response of NKT cells has been studied extensively by multiple groups with α-GalCer that has been proven to be a unique type of adjuvant for vaccine development (7). New analogues of α-GalCer are being synthesized to search for new NKT cell agonists that may have superior properties for the treatment of autoimmune and inflammatory diseases. One of these, α-C-GalCer was found to be more potent in helping mice to defend against mouse malaria and B16 melanoma by inducing a more prolonged IL-12 and IFN-γ response (14). Moreover, α-C-GalCer was reported bind more stably to DCs than α-GalCer, and α-C-GalCer-loaded DCs induced higher levels and longer lasting IFN-γ-producing NKT cell responses and more effective adaptive protective T-cell-mediated immunity (21).. iGb3, the ...
We have made the observation that anti-CD1d mAbs may be useful antitumor agents when used in combination with chemoimmunotherapies and in the context of large established s.c. tumors, like 4T1 and CT26L5, that are controlled by regulatory type II NKT cells. 1DMab (anti-DR5/anti-CD1d/anti-CD137) therapy was more efficacious than TriMab therapy in the eradication of CT26L5 and 4T1 tumors, but less effective against R331 tumors. In this manner, anti-CD1d mAbs are a very effective substitute for anti-CD40 mAbs, particularly when tumors are regulated by CD1d and type II NKT cells. There were no adverse toxicities detected after 1DMab therapy. 1DMab-mediated tumor suppression was dependent on CD8+ T cells, IFN-γ, and CD1d in all three tumor models examined. In seeking an explanation as to why 1DMab was more effective than TriMab in the 4T1 and CT26L5 tumor models, we revealed that although 1DMab and TriMab therapy yielded similarly increased proportions of CD8+ T cells in the tumor DLN producing ...
Natural Killer T (NKT) cells are a subset of mature T lymphocytes which have been shown to play a major role in controlling immune responses. Recently, it has become evident that the antigen receptor expressed by NKT cells recognize glycolipids presented by CD1d, a major-histocompatibility complex class I-like molecule expressed on dendritic cells, monocytes, and a subgroup of B cells. Via recognition of glycolipids by NKT cells, various cytokines are released which influence other cells of the immune system. A synthetic α-galactosylceramide, KRN 7000, was shown to possess anti-tumor and immunostimulatory activities. To further understand the significant biological activities of glycolipids, in this thesis we describe the synthesis of an OCH analogue, α-S-GalCer, and a series of carbohydrate modified analogues of KRN 7000. ^
Wilbur, S; De, L; and Bonavida, B, "The role of ia and inappropriate h-2d antigens on sjl/j reticulum cell sarcomas in syngeneic proliferation and recognition. Abstr." (1980). Subject Strain Bibliography 1980. 1091 ...
The CD1d/ -GalCer Dextramers displays CD1d molecules loaded with -GalCer, or without a unique lipid, unloaded CD1d. Both human and mouse CD1d can stain cells of mouse and human origen, although not identical NKT cell populations are found between species.. Features;. • Superior separation. • High stability. • Reproducible results. • Quality controled. • Available with FITC, PE and APC.. CD1d/ -GalCer Dextramer:. Human CD1d: Cat. No. XD8002. Mouse CD1d: Cat. No. YD8002. * The CD1d/ -GalCer Dextramer displays CD1d molecules loaded with the glyco-lipid, -GalCer. CD1d/unloaded Dextramer:. Human CD1d: Cat. No. XD8001. Mouse CD1d: Cat. No. YD8001. * Load your lipid of interest to generate a unique CD1d/lipid Dextramer. Can be used as negative control reagent. The CD1d/unloaded Dextramer reagent displays CD1d molecules without loaded lipid antigen.. Protocol for loading of lipids into CD1d_unloaded Dextramers (PDF). Human CD1d Dextramer labled with either FITC, PE AND APC. ...
In this study, we have shown that CD1d-restricted glycolipid ligands reactive with iNKT cells effectively substitute for anti-CD40 mAbs and can reject established experimental mouse breast and renal tumors when used in combination with anti-DR5 and anti-4-1BB mAbs. This combination, which we termed NKTMab therapy, induced tumor rejection that required CD4+ and CD8+ T cells, NKT cells, and the cytokine IFN-γ. NKTMab therapy containing either α-GC or α-c-GC at higher concentrations induced similar rates of tumor rejection in mice; however, toxicity was observed at the highest doses of α-GC (,250 ng/injection). By contrast, very low doses of α-c-GC (25 ng/injection) retained considerable antitumor activity when used in combination with anti-DR5/anti-4-1BB, and thus, α-c-GC showed a considerably greater therapeutic index. Given the shown toxicities of CD40 agonists in humans and mice ( 13, 16), this study illustrates the alternative of using NKT cell agonists that in synergy with an ...
Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficient mice showed a complete absence of mature NKT cells in the thymus and periphery. Mechanistically, miR-181 modulated expression of the phosphatase PTEN to control PI3K signaling, which was a primary stimulus for anabolic metabolism in immune cells. Thus miR-181-deficient mice also showed severe defects in lymphoid development and T cell homeostasis associated with impaired PI3K signaling. These results uncover miR-181 as essential for NKT cell development and establish this family of miRNAs as central regulators of PI3K signaling and global metabolic fitness during development and homeostasis. ...
The researchers goal was to create a therapy that would permanently boost the bodys ability to naturally produce more iNKT cells.
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Glycolipid ligands for invariant natural killer T cells (iNKT cells) are loaded onto CD1d molecules in the late endosome/lysosome. Accumulation of glycosphingolipids (GSLs) in lysosomal storage diseases could potentially influence endogenous and exogenous lipid loading and/or presentation and, thus, affect iNKT cell selection or function. The percentages and frequency of iNKT cells were reduced in multiple mouse models of lysosomal GSL storage disease, irrespective of the specific genetic defect or lipid species stored. Reduced numbers of iNKT cells resulted in the absence of cytokine production in response to alpha-galactosylceramide (alpha-GalCer) and reduced iNKT cell-mediated lysis of wild-type targets loaded with alpha-GalCer. The reduction in iNKT cells did not result from defective expression of CD1d or a lack of antigen-presenting cells. Although H-2 restricted CD4(+) T cell responses were generally unaffected, processing of a lysosome-dependent analogue of alpha-GalCer was impaired in all the
Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells; for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose
Sulfatides are innate glycosphingolipids shown to activate a subpopulation of type II NKT cells. Their activation has been reported to sometimes have antagonistic roles to those of type I NKT cells in some disease models. This has sparked a lot of interest in the synthesis of natural and unnatural sulfatides for an examination of their influence on NKT cell responses. The design, synthesis and evaluation of type II NKT cell activation of several sulfatide ligands are described in this thesis. A two-step methodology has been developed for the rapid assembly of disubstituted β-lactones. The first step is olefin cross metathesis (CM) of a-methylene-β-lactones with various alkene cross partners to furnish a-alkylidine-β-lactones. These are subsequently diastereoselectively reduced. A diverse library of β-lactones, including (±)-nocardiolactone has been prepared. Combining this approach with competitive activity-based protein profiling (ABPP) identified lead β-lactone inhibitors for several serine
Background: NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. Objective: To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as activated T lymphocytes, in tumor draining lymph nodes (TDLNs) of patients with breast cancer (BC) and their association with different clinic-pathological features of the patients. Methods: Axillary lymph nodes were obtained from 30 Iranian women with breast cancer. After routine pathological evaluations, mononuclear cells were separated from their lymph nodes and incubated with appropriate fluorochrome conjugated monoclonal antibodies specific for CD3, HLA-DR, CD16/56, and Vα24Jα18-TCR. Data were collected on a four-color flow cytometer and analyzed by CellQuest software. Results: The mean percentages of NK (CD3-CD16/56+), NKT (CD3+CD16/56+) and iNKT (Vα24Jα18-TCR+) cells in TDLNs mononuclear cells
To make their discovery, scientists infected three groups of mice with H1N1 flu virus. (Note: this is NOT the H5N1 flu virus that has been at the center of recent controversy.) The first group included normal mice; the second group was devoid of natural killer T cells, and the third was given a treatment that specifically activated natural killer T cells. Researchers observed the outcome of flu infection and found that the mice without natural killer T cells did worst, and those with activated killer T cells did best. Mice that lacked natural killer T cells had increased amounts of monocytes in the lungs, and severe lung injury similar to those seen in Spanish flu and lethal swine flu. Using highly-sensitive fluorescent antibody technology, this study was one of the first to document the sequential changes in innate immune response in the lungs during severe flu infection. These findings essentially provide a "road map" of the chronological changes in the lungs during severe flu infection. ...
Natural Killer (NK) cells were initially named based on their propensity for cytolytic function in the absence of any specific kind of activation. NK cells are an important part of innate immunity, defending the body against both virally infected cells and tumor cells. Natural Killer T (NKT) cells represent a special hybrid of T cell and NK cells. They express a T cell receptor complex and several NK cell markers. Unlike T cells, they mainly recognize lipid antigen presented by CD1d and not MHCs. NKT cells are capable of producing both Th1 and Th2-related cytokines. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury. This OX40/NKT pyroptosis pathway also plays a key role in concanavalin A-induced murine hepatitis. Mechanistically, we demonstrated that liver iNKT cells express high levels of caspase 1 and that OX40 stimulation activates caspase 1 via TNF receptor-associated factor 6-mediated recruitment of the paracaspase MALT1. We also found that activation of caspase 1 in iNKT cells results in processing of ...
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury. This OX40/NKT pyroptosis pathway also plays a key role in concanavalin A-induced murine hepatitis. Mechanistically, we demonstrated that liver iNKT cells express high levels of caspase 1 and that OX40 stimulation activates caspase 1 via TNF receptor-associated factor 6-mediated recruitment of the paracaspase MALT1. We also found that activation of caspase 1 in iNKT cells results in processing of ...
Natural killer T (NKT) cells, which comprise a minor population of T cells in primary and secondary lymphoid organs, possess phenotypic characteristics of both NK and T cells. NKT cells respond to various external stimuli by an early burst of cytokines, including IL-4 and IFN-. Thus, a key immunoregulatory role has been attributed to them. Autoimmune diseases, especially type I diabetes (TID), may be caused by dysregulation of the immune system, which leads to hyporesponsiveness of regulatory T helper 2 (Th2) cells and promotion of autoimmune Th1 cells. Furthermore, several lines of evidence exist to support the notion that an NKT cell deficiency in individuals at risk of TID may be causal to TID. As a result, targeting NKT cells using immunotherapeutic agents may prove beneficial in the prevention or recurrence of TID. Indeed, our data demonstrate that stimulation of NKT cells with a specific ligand prevents the onset and recurrence of TID in non-obese diabetic (NOD) mice ...
To optimize vaccination strategies, it is important to use protocols that can jump-start immune responses by harnessing cells of the innate immune system to assist the expansion of antigen-specific B and T cells. In this Review, we discuss the evidence indicating that invariant natural killer T (iNKT) cells can positively modulate dendritic cells and B cells, and that their pharmacological activation in the presence of antigenic proteins can enhance antigen-specific B- and T-cell responses. In addition, we describe structural and kinetic analyses that assist in the design of optimal iNKT-cell agonists that could be used in the clinical setting as vaccine adjuvants.
Natural Killer (NK) and Natural Killer T (NKT) cells are unique lymphocytes mainly involved with innate immunity. NK cells are capable of targeting tumor cells and virus-infected cells for destruction. They routinely check target cells for the expression of particular markers, which guide them toward activation or tolerance. Natural Killer T cells are a unique hybrid, sharing qualities of both T cells and Natural Killer cells. They emigrate from the thymus, displaying NK markers and harboring the potential to launch aggressive Th1 or Th2 cytokine release. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
Abstract Natural killer T (NKT) cells are important regulatory lymphocytes that have been shown in mouse studies, to have a crucial role in promoting immunity to tumours, bacteria ..
The method to generate highly antigen specific iPSC-derived killer T cells is established by Dr. Shin Kaneko, an associate professor and a leading scientist of immunotherapy using iPSC-derived killer T cells, in Center for iPS cell Research and Application, Kyoto University. The iPSC technology allows Thyas to stably supply a large quantity of tumor-specific or virus-specific T cells that have high proliferative capacity and potent killing activity. As of today, no other method produces highly antigen specific iPSC-derived killer T cells.. Novel immunotherapies have demonstrated significant benefits to cancer patients, however, the use of those is limited due to severe adverse events and therapy resistance. Thyas iPS-derived T cell products are expected to be safe and highly effective to many patients with cancers and infectious diseases. Therefore, the approach has a great clinical advantage.. About Thyas ...
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium ...
NKT cells induce cell death in cancer cells in the similar mechanism with NK cells, but their direct cytotoxic activity is limited because they are only found in small quantities in the body. However, NKT cells do have the ability to produce large amounts of cytokine (IFN-γ, etc.). NKT cells contribute to the activate NK cells and other cells representing innate immune system and cytotoxic T cells(cytotoxic T lymphocyte: CTL) representing acquired immune system through production of IFN-γ and other helper T (Th) 1 cytokines; stimulate antibody production from B cell and induction of allergic inflammation through production of IL-4 and other Th2 cytokines; and inhibit non-allergic diseases through IL-17 production. As around 90% of NKT cells work to prevent infections, and due to the ability of NKT cells to immediately produce large amounts of cytokine upon antigen recognition without the need for clonal growth, NKT cells are currently considered to play the role of an adjuvant that activates ...
Transfer of antigen presenting cells in vivo is a method used by immunologists to examine the potency of antigen presentation by a selected population of cells. This method is most commonly used to analyze presentation of protein antigens to MHC class I or II restricted T cells, but it can also be used for studies of nonconventional antigens such as CD1-presented lipids. In a recent study focusing on CD1d-restricted glycolipid antigen presentation to Natural Killer T cells, we compared antigen presenting properties of splenic B cells, CD8αPos dendritc cells (DCs) and CD8αNeg DCs (Arora et al., 2014). This protocol describes the detailed method used for isolation of these cell populations, and their transfer into recipient mice to analyze their antigen presenting properties.As a percentage of total mononuclear cells, an average spleen contains approximately 1-3% myeloid dendritic cells (DCs). In absolute numbers, this translates to approximately 0.6-1.8 x 106 DCs. To enhance the number of DCs in
Natural Killer T (NKT) cells are potent, regulatory T cells that have been shown to be intimately involved in the bodys response to infection and tumor progres...
Strong increase of protective serum cytokines after injection of B7-H1−/− DC injection is mainly produced by type II NKT cells.A) Splenocytes from WT and J
If you watched Wall-E you likely laughed at the depiction of hugely obese people riding around in hover cars drinking Big Gulps - surely a science that could create the technology to generate an entire artificial world could solve how to drink Big Gulps without turning ban happy like California or New York. |!-- --|…
Also called TCRAV7S2 according to the nomenclature from Arden et al. The iValpha7.2 segment in humans is an evolutionarily conserved invariant TCRalpha chain, expressed in mucosal associated invariant T (MAIT) cells, also called mNKT. MAIT cells are abundant in human blood (1-8% of T cells vs. 0.01-1% for NKT cells), the intestinal mucosa and mesenteric lymph nodes (MLN). MAIT cells are evolutionarily conserved innate-like T cells with anti-microbial properties. They are apparently also involved in non-infectious inflammatory disorders and in autoimmune inflammatory lesions. MAIT cells were found to specifically accumulate in the lamina propria (LP) of the intestine. This suggests that these cells may, in fact, be directed to microbial antigens presented by MR1 molecules, having a role of natural killer T cells (mNKT cells) in intestinal immunology. mNKT cells are a subset of non-conventional T cells recognizing endogenous and / or exogenous glycolipid antigens when presented by the major ...
Sigma-Aldrich offers abstracts and full-text articles by [Florence Robert-Gangneux, Anne-Sophie Drogoul, Octavie Rostan, Claire Piquet-Pellorce, Jérome Cayon, Mariette Lisbonne, André Herbelin, Hugues Gascan, Claude Guiguen, Michel Samson, Jean-Pierre Gangneux].
Discussion of the Immune System including T cells, B cells, macrophages, Natural Killer T cells, bone marrow, chemokines, cytokines, innate immunity, blood types, immune response, inflammation
SHIKAWA Hiroyuki , HISAEDA Hajime , TANIGUCHI Masaru , NAKAYAMA Toshinori , SAKAI Tohru , MAEKAWA Yoichi , NAKANO Yoko , ZHANG Manxin , ZHANG Tianqian , NISHITANI Masaki , TAKASHIMA Miwa , HIMENO Kunisuke International immunology 12(9), 1267-1274, 2000 参考文献49件 被引用文献3件 ...
Erythrocytes bearing the Rh(D) antigen have an Mr 30,000 integral membrane protein which can be surface-labeled with 125I and can be quantitatively immunoprecipitated from Triton X-100-solubilized spectrin-depleted membrane ...
gap, y:= [ [ 1, 0, 0, 0, 0, 0, 0 ], [ 2/3, -1/3, 2/3, -1/3, -1/3, -1/3, -1/3 ], [ 2/3, -1/3, -1/3, -1/3, 2/3, -1/3, -1/3 ], [ 1/3, 1/3, 1/3, -2/3, 1/3, 1/3, -2/3 ], [ 2/3, 2/3, -1/3, -1/3, -1/3, -1/3, -1/3 ], [ 1/3, 1/3, 1/3, -2/3, 1/3, -2/3, 1/3 ], [ 1/3, 1/3, 1/3, 1/3, 1/3, -2/3, -2/3 ...
Background: Invariant natural killer cells (iNKT) are an important immunoregulatory T cell subset. Currently several flow cytometry-based approaches exist for the identifi-cation of iNKT cells, which rely on using the 6B11 monoclonal antibody or a combina-tion of anti-Vα24 and anti-Vβ11 antibodies. Objective: The aim of this study was to compare the ability of two flow cytometry-based methods for detecting the frequency of circulating iNKT cells. Methods: The frequency of iNKT cells was detected in the pe-ripheral blood of 37 healthy adult donors by flow cytometry using the 6B11 antibody or a combination of anti-Vα24 and anti-Vβ11 antibodies. Results: The frequency of iNKT cells detected by 6B11 antibody or by combination of anti-Vα24 and anti-Vβ11 anti-bodies was significantly different (0.54% vs. 0.31%, respectively, p|0.001) but the val-ues were highly correlated (Spearman r = 0.742, p|0.0001). Conclusion: The results of this study indicate that different combinations of mAbs detect different
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane. Autophagosomes intersect with MIICs and autophagy-related proteins are known to support antigen loading for increased CD4(+) T cell immunity. Here, we report that mice with dendritic cell (DC)-specific deletion of the essential autophagy gene Atg5 showed better CD1D1-restricted glycolipid presentation in vivo. These effects led to enhanced iNKT cell cytokine production upon antigen recognition and lower bacterial loads ...
Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally
Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally
Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α
Objectives Data from rodent models indicate that invariant natural killer T (iNKT) cells are key regulators of many immune responses including autoimmune arthritis, but their role in human diseases is unclear. The aims of this study are to determine whether iNKT cell frequency and function are altered in patients with rheumatoid arthritis (RA), and the clinical significance of such iNKT cell abnormalities.. Methods Peripheral blood iNKT cell frequency and proliferative response to an iNKT cell-specific agonist, α-galactosylceramide were measured in 46 RA patients (including 23 untreated, newly diagnosed patients), 22 healthy controls and 27 patients presenting with recent-onset joint pain. The relationship between iNKT cell frequency and clinical characteristics and the effects of immunosuppressive treatment was examined.. Results Compared with healthy controls, RA patients had a decreased frequency of peripheral blood iNKT cells (median 0.001% vs 0.021%, p,0.001) and the proliferative response ...
Natural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2α in T/NKT cells and found that HIF-2α knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2α knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1+ cell depletion or Fas ligand blockade. Compared with wild-type NKT cells, HIF-2α−/− NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. ...
Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome
Adipose tissue inflammation is an important factor in obesity that promotes insulin resistance. Among various cell types in adipose tissue, immune cells actively regulate inflammatory responses and affect whole-body energy metabolism. In particular, invariant Natural Killer T (iNKT) cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesity-induced inflammation in adipose tissue. However, the molecular mechanisms by which adipose iNKT cells become activated and mediate anti-inflammatory roles in obese adipose tissue have not been thoroughly understood yet. In the present study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. Accordingly, adipocyte-specific CD1d knockout (CD1dADKO) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide (α-GC)-induced iNKT cell activation. ...
Alpha-galactosylceramide (α-GalCer) is a glycolipid that can be loaded into MHC-class-I-related CD1d molecules by dendritic cells and has been shown to stimulate invariant natural killer T (iNKT) cells. iNKT cells have emerged as important contributors to the regulation of immune responses, T cell activation, and anti-tumor activity. Through this activation cascade, α-GalCer exerts potent anti-tumoral and immune regulatory activities. However, the limitations were found in clinical application that (1) iNKT cells failed to produce cytokines and proliferate when additional doses of α-GalCer were given by systemic route and (2) poor hydrophilicity of α-GalCer. In this project, α-GalCer was incorporated into the lipid bilayer of the liposome, while the galactose molecular was expressed on the surface of the liposome to form a targeting liposome antigen-carrier with immunemodulatory effect. Thus, α-GalCer-incorporated liposome is capable of improving the delivery of antigen to ...
Beyaz S, Kim JH, Pinello L, Xifaras ME, Hu Y, Huang J, Kerenyi MA, Das PP, Barnitz RA, Herault A, Dogum R, Haining WN, Yilmaz ÖH, Passegue E, Yuan GC, Orkin SH, Winau F. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol. 2017 Feb; 18(2):184-195 ...
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Mayo Lab Director/Consultant approval is required prior to ordering test, contact Mayo Medical Laboratories.. This assay does not measure cell-surface or intracellular proteins on NK/NKT cell subsets. Order NKSP / Natural Killer (NK)/Natural Killer T (NKT) Cell Subset Panel.. A minimum CD45 lymph count (as measured by flow cytometry in the laboratory) is required to report this test. If that requirement is not met (eg, patients with severe lymphopenia), the test will be canceled and an alternate test will be suggested (TBBS / T- and B-Cell Quantitation by Flow Cytometry).. ...
NKT cells play a protective role in ischemia reperfusion (IR) injury, of which the trafficking in the body and recruitment in injured organs can be influenced by immunosuppressive therapy. Therefore, we investigated the effects of rapamycin on kidneys exposed to IR injury in early stage and on trafficking of NKT cells in a murine model. Balb/c mice were subjected to kidney 30 min ischemia followed by 24 h reperfusion. Rapamycin (2.5 ml/kg) was administered by gavage daily, starting 1 day before the operation. Renal function and histological changes were assessed. The proportion of NKT cells in peripheral blood, spleen and kidney was detected by flow cytometry. The chemokines and corresponding receptor involved in NKT cell trafficking were determined by RT-PCR and flow cytometry respectively. Rapamycin significantly improved renal function and ameliorated histological injury. In rapamycin-treated group, the proportion of NKT cells in spleen was significantly decreased but increased in peripheral blood
b) Either α-GC (2 μg) or PBS was i.p. injected into B6 WT mice. Sixteen hours later, the total DCs or NKDC-depleted DCs isolated from these mice were used as effector cells for the cytotoxicity assay. The efficiency of depletion is shown in the upper panel. CFSE-labeled YAC-1 tumor cells were used as target cells. Effector cells were co-cultured with 2 × 104 target cells at the indicated ratios. Cytotoxicity at the 27 : 1 E : T ratio is displayed in the lower panel. Cytotoxicity was evaluated by calculating the percentage of 7-AAD+ (dead) cells compared to CFSE+ target cells. The mean values ± SD are shown ...
The purpose of this study is to evaluate the efficacy and safety of PD-1 blockade pembrolizumab for patients with relapsed or refractory Natural Killer(NK)/T
Results The clonal repertoire of iNKT cells in healthy controls shows a broad distribution with regard to iNKT receptor affinity for CD1d. In contrast, the repertoire is highly significantly shifted towards lower-affinity iNKT clones in age-matched early RA. This shift correlates with DAS28. Analysis of untreated vs treated early RA patients shows that the iNKT repertoire is "restored to normal" in the DMARD group, and this correlates with DAS28. CD1d expression on antigen-presenting cells was not different between groups. iNKT cells in all early RA patients exhibited a bias in cytokine secretion towards Th1 cytokines, independent of CD1 antigen processing.. ...
The immune response is a dynamic process that starts with a rapid response of innate immunity and passes through multiple phases controlled by cellular and molecular components of the immune system, ending with the development of specific and powerful adaptive immunity. iNKT cells consist of a subset of innate-like lymphocytes that are intermediates between innate and adaptive immunity and play important roles in the initiation and regulation of immune responses to tumors and infectious organisms (1). iNKT cells have attracted attention because of their unique ability to rapidly produce large amounts of IFN-γ, which induces the cytotoxic activities mediated by natural killer and CD8+ T cells (22, 33). Activation of iNKT cells by the administration of α-GC or α-GC-pulsed dendritic cells has been considered one of the most potent and promising strategies for the eradication of tumors, as several preclinical studies in animal models in addition to clinical trials have shown encouraging results ...
NISHIO Shoji , YAMADA Naoko , OHYAMA Hideki , YAMANEGI Koji , NAKASHO Keiji , HATA Masaki , NAKAMURA Yoshiteru , FUKUNAGA Satoru , FUTANI Hiroyuki , YOSHIYA Shinichi , UEDA Haruyasu , TANIGUCHI Masaru , OKAMURA Haruki , TERADA Nobuyuki Cancer science 99(1), 113-120, 2008-01-10 医中誌Web 参考文献49件 ...
Structure: Monomer
Secreted by: Activated T cells, Dendritic Cells, Natural Killer cells, Natural Killer T cells
Functions: Proliferation of B cell, B cells and NK cells, differentiation of Treg and NK cells
Disease areas: Inflammatory and autoimmune diseases, X-linked severe combined immunodeficiency I
Many types of innate (natural killer cells, natural killer T cells, and Kupffer cells/macrophages) and adaptive (T cells and B cells) immune cells are enriched ...
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Blood cell donations could be used to treat transplant patients with a particular form of cancer, according to a Cancer Research UK study reported in the journal Blood.
The field of immunology has a few quirks. Im sure this is no different than other fields of study, but one of the most puzzling (and sometimes infuriating) of these quirks is an obsession with categorizing different types of cells. Case in point, a recent paper in Nature Immunology: A semi-invariant Vα10+ T cell antigen…. ...
Last week I talked some general issues about autoimmunity, and gave a brief background on NKT cells. Today Ill talk about the paper that spawned that discussion. ((Mattner, J., Savage, P., Leung, P., Oertelt, S., Wang, V., Trivedi, O., Scanlon, S., Pendem, K., Teyton, L., Hart, J. (2008). Liver Autoimmunity Triggered
Find out about the science and chemistry of Liothyronine (Cytomel, Tertroxin), see colourful images of Liothyronine and explore interactive 3D molecules of Liothyronine
Gabazza EC1 and Takei Y2. 1. Department of immunology, Mie University Graduate School of Medicine, Tsu, Mie, Japan 2. Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. Alcohol consumption is a major cause of liver injury but the mechanisms are not completely understood. Protein S (PS) is an anticoagulant glycoprotein with multiple functions. The role of PS in liver injury is unknown. This study investigated the role of PS in acute alcoholic hepatitis. Methods: A mouse overexpressing human PS (hPS-TG) was generated in which acute hepatitis was induced by intraperitoneal injection of ethanol. The levels of serum liver enzymes, liver tissue inflammatory cytokines and the degree of hepatic steatosis were significantly increased in hPS-TG mice treated with ethanol compared with ethanol-treated wild type (WT) mice. Cell expansion, activation and inhibition of apoptosis were significantly augmented in natural killer T (NKT) cells from hPS-TG ...
Stimulation with αGalCer also led to NK cell (CD3−CD49b+NK1.1+) activation and cytokine production. We therefore analyzed the expression of CD69 on NK cells and their production of pro-inflammatory cytokines in FV-infected mice after αGalCer administration (Additional file 2: Figure S2 D). We detected an activation of NK cells post FV infection, which was significantly enhanced post αGalCer therapy (Additional file 2: Figure S2 D, CD69, black bars). The αGalCer treatment also increased the percentages of TNFα produced by NK cells (Additional file 2: Figure S2 D, gray bars). IFNγ production by NK cells was induced by FV infection, but was not further enhanced post αGalCer administration (Additional file 2: Figure S2 D, white bars). Thus, secondary effects of NKT cell stimulation on NK cells may partly contribute to the anti-retroviral effects after αGalCer therapy.. In this report, we analyzed the impact of NKT cells on the control of viral replication during initial phase of acute FV ...
Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell-deficient (CD1d-/- and Jα18-/-) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17-/- mice nor in
The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(α1→2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor. A lysosomal enzyme, α-galactosidase A, was responsible for the processing of Gal(α1→2)GalCer to generate the antigenic monosaccharide epitope. These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids. ...
The CD57 test (only from Labcorp) measures a subset of NKT cells. These are Natural Killer T Cells. These T cells are actors in the innate immune response. In other words, these cells automatically attack what our immune system sees as foreign invaders. Our immune systems are naturally smart (anthropomorphically). They have pattern recognition cells which can determine tissues/cells that belong in our bodies from things (like bacteria) that do not belong in our bodies. The second part of the immune system, the acquired immune system relates to a complex set of reactions by which the immune system learns to make specific antibodies to attack the foreign invader. In some situations only the innate immune system is in play. Primarily this occurs when the "invaders" are intracellular. The acquired responses just dont work here. In the case of Lyme disease it is the intracellula- L-forms which are attacked by the NKT cells. When the CD57 count is low it would appear these cells are busy combating ...
The CD57 test (only from Labcorp) measures a subset of NKT cells. These are Natural Killer T Cells. These T cells are actors in the innate immune response. In other words, these cells automatically attack what our immune system sees as foreign invaders. Our immune systems are naturally smart (anthropomorphically). They have pattern recognition cells which can determine tissues/cells that belong in our bodies from things (like bacteria) that do not belong in our bodies. The second part of the immune system, the acquired immune system relates to a complex set of reactions by which the immune system learns to make specific antibodies to attack the foreign invader. In some situations only the innate immune system is in play. Primarily this occurs when the "invaders" are intracellular. The acquired responses just dont work here. In the case of Lyme disease it is the intracellula- L-forms which are attacked by the NKT cells. When the CD57 count is low it would appear these cells are busy combating ...
T cells consist of two major groups: CD4-positive T helper cells (who help other immune cells in mounting an effective response) and CD8-positive killer T cells. HIV infects and destroys CD4-positive cells, leaving patients with a crippled immune system. Throughout the course of HIV disease, however, patients have high levels of HIV-specific killer T cells. Early after initial infection, these cells are able to effectively kill the virus and reduce viral load. On the other hand, during the later stage of disease killer T cells, while still present, seem no longer able to control the virus. In an article in the November 4 issue of the Journal of Clinical Investigation, Premlata Shankar and colleagues from the Center for Blood Research at Harvard Medical School suggest why this might be the case ...
The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well referred to. of Bregs and review our current understanding of Bregs and their inhibition of anti-tumor resistant replies in murine growth versions and tumor sufferers. research, in the past due 1990s, displaying that the adoptive transfer of turned on splenic N cells activated patience and the difference of Testosterone levels cells into suppressor Testosterone levels cells in unsuspecting receiver rodents.33, 34 After these seminal findings, which designated a function for Temsirolimus suppressor B cells in resistant patience, the term regulatory B cells (Bregs) was not coined until nearly 30 years later on, by Bhan and Mizoguchi.35 Mizoguchi et al identified a population of gut-associated, IL-10-creating, CD1d-expressing B cells that suppressed the development of colitis-related intestinal inflammation by downregulating inflammatory cascades.35 However, despite ...
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Eddie A. James is the author of this article in the Journal of Visualized Experiments: Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
Neuropathology in multiple sclerosis is closely linked to presence of macrophages in the CNS. Both M1 (inflammatory) and M2 (alternatively activated, noninflammatory) macrophages are found in the inflamed CNS and thought to differentiate from infiltrating monocytes. It is unclear whether the balance of M1 and M2 macrophages can be altered and whether this affects disease outcome. We show in this article that Ly6C(hi) inflammatory monocytes are the early and dominant infiltrating cells in the CNS during experimental autoimmune encephalomyelitis, a model for the acute phase of multiple sclerosis. Activation of invariant NKT (iNKT) cells reduced the frequency of Ly6C(hi) monocytes and increased the proportion of M2 macrophages in the CNS with associated improvement in neurologic impairment. In contrast, iNKT-deficient mice showed higher numbers of Ly6C(hi) monocytes, reduced M2, and much more severe disease. Adoptive transfer of M2-enriched cells to iNKT-deficient mice markedly improved neurologic
Natural killer (NK) cells are derived from pluripotent hematopoietic stem cell precursors, but develop independently of the thymus. They comprise a key lymphocyte subset (approximately 10%-15% of peripheral blood mononuclear cells) and are a constituent of the innate immune system, since these cells do not rearrange their germline DNA to obtain specificity. NK cells serve an important role in host defense against viral infections, as well as tumor surveillance. They are also a component of the adaptive immune response through cytokine production. NK cell functions are governed by a balance between activating receptors and inhibitory receptors.. NK cells are identified by expression of different cell-surface receptors and they are not a homogeneous population.(1) In general, the most common combination of surface markers used to identify the majority of NK cells is the absence of CD3 (CD3-), along with expression of CD56 (neural cell adhesion molecule) and CD16 (low-affinity IgG Fc receptor-Fc ...
In the past decade, the suppressive effects, mainly through the secretion of IL-10, of regulatory B cells on inflammatory responses have been reported in a variety of immune disorders (33-36). Additionally, immune regulation through the interaction of immune cells with the intrinsic phenotype of regulatory B cells (e.g., CD1dhiCD5+, T2-MZP, Tim-1+, and CD9+) were demonstrated in various diseases, and it plays a critical role in autoimmune diseases (37). In recent studies, functional studies in cancer diseases are emerging (38-40). In particular, the change of the distribution of regulatory B cells in cancer tissue is considered to one of important indicators (8-10). Emerging evidence suggests that regulatory B cells suppress effector immune cells including IFN-γ-producing cytotoxicity cells in various cancer diseases through the secretion of IL-10 (11). Although regulatory B cells have to play the suppressive role on the effector function of T cells in autoimmune diseases to cure diseases (41), ...
Invariant natural killer T (iNKT) cells promote immune responses to various pathogens, but exactly how iNKT cells control antiviral responses is unclear. Here, we showed that iNKT cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (LCMV). Indeed, iNKT cells inhibited viral replication in the pancreas and liver but not in the spleen. In the pancreas, iNKT cells expressed the OX40 molecule and promoted type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through OX40-OX40 ligand interaction. Subsequently, this iNKT cell-pDC cooperation attenuated the antiviral adaptive immune response in the pancreas but not in the spleen. The dampening of pancreatic anti-LCMV CD8(+) T cell response prevented tissue damage in transgenic mice expressing LCMV protein in islet beta cells. Thus, this study identifies pDCs as an essential partner of iNKT cells for mounting an efficient, nondeleterious antiviral response in peripheral tissue.
NKT cells are a regulatory subset of T lymphocytes with immune modulatory effects and an important role in anti-tumor immunity. The feasibility of ex-vivo education of NKT cells has recently been demonstrated. To evaluate the anti-tumor effect of ex-vivo immune-modulated NKT lymphocytes in a murine model of hepatocellular carcinoma. Athymic Balb/C mice were sublethally irradiated and transplanted with human Hep3B HCC. NKT cells prepared from immunocompetent Balb/C mice were pulsed ex vivo with HCC-derived antigens (Group A), Hep3B cells (group B) or BSA (group C), and adoptively transferred into HCC harboring mice (1 x 0(6) NKT cells per mouse). Group D mice did not undergo NKT cell transplantation. Group E mice were transplanted with 1 x 10(6) NKT cells from HBV-immunized donors. Mice were followed for tumor size and weight. To determine the mechanism of the anti-tumor effect, intrasplenic lymphocyte populations were analyzed by FACS for NKT, CD4+ and CD8+ lymphocyte subpopulations; STAT 1, 4 and 6
Invariant natural killer T (iNKT) cells are essential components of immune system responses during many chronic diseases, yet their surface area phenotypes, subset distribution, and polyfunctional capability within this environment are unknown largely. activation markers Compact disc69 and Compact disc56. Functionally, both total IFN-gamma+ as well as the dual-functional IFN-gamma+ TNF-alpha+ iNKT cells had been reduced in sarcoidosis topics and these useful flaws correlated with total iNKT circulating frequencies. As the increased loss of polyfunctionality can reveal useful exhaustion, we assessed buy 72496-41-4 the top antigens PD-1 and Compact disc57 and discovered that amounts inversely correlated with dual-functional iNKT cell percentages. These results reveal that, comparable to traditional T cells, iNKT cells may go through useful exhaustion, which circulating iNKT frequencies reveal these flaws. PD-1 antagonists might therefore be appealing therapeutic applicants for sarcoidosis and ...

Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers | JEMTracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers | JEM

1999) CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science. 283:225-229, pmid: ... 1998) CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. J. Exp. Med. 188:1529-1534 ... Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers. Jennifer L. Matsuda, Olga V. ... Dimeric CD1d-α-GalCer Complexes.. Soluble recombinant mCD1d1 and human (h)CD1d proteins expressed in Drosophila SC2 cells have ...
more infohttp://jem.rupress.org/content/192/5/741?ijkey=7ccaef30789fdfbe98e851e5cebc5f0b5f9864e6&keytype2=tf_ipsecsha

BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand |...BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand |...

BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand. ... BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand ... BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand ... BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand ...
more infohttp://www.jimmunol.org/content/early/2013/06/22/jimmunol.1300263

B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in...B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in...

... iNKT cells have an antigen-experienced phenotype and can respond very rapidly to CD1d-presented antigens without the need for ... 1998) CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. J Exp Med 188:1529-1534.. ... 2001) Glycolipid antigen processing for presentation by CD1d molecules. Science 291:664-667.. ... B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in ...
more infohttps://www.pnas.org/content/105/24/8345?ijkey=c27391fcc60faedf3033be39701b19bd5d8cd34a&keytype2=tf_ipsecsha

Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells.  - PubMed - NCBILow expression level but potent antigen presenting function of CD1d on monocyte lineage cells. - PubMed - NCBI

CD1d is a key antigen-presenting molecule involved in the selection and activation of a highly conserved T cell subset known as ... Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells.. Spada FM1, Borriello F, Sugita ... In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of ... and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. Overall, these ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/11093166?dopt=Abstract

Glycolipid Antigen Processing for Presentation by CD1d Molecules | ScienceGlycolipid Antigen Processing for Presentation by CD1d Molecules | Science

Glycolipid Antigen Processing for Presentation by CD1d Molecules Message Subject. (Your Name) has forwarded a page to you from ... Glycolipid Antigen Processing for Presentation by CD1d Molecules. By Theodore I. Prigozy, Olga Naidenko, Pankaj Qasba, Dirk ... Glycolipid Antigen Processing for Presentation by CD1d Molecules. By Theodore I. Prigozy, Olga Naidenko, Pankaj Qasba, Dirk ... The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to ...
more infohttps://science.sciencemag.org/content/291/5504/664?ijkey=235af4cb645ab4bd0d08c006ab35a095c6c8d7fc&keytype2=tf_ipsecsha

Lipid binding orientation within CD1d affects recognition of Borrelia burgorferi antigens by NKT cells | PNASLipid binding orientation within CD1d affects recognition of Borrelia burgorferi antigens by NKT cells | PNAS

Cell-free antigen presentation assay.. Antigen presentation experiments using wild-type or point-mutated CD1d molecules and V ... Mice express only CD1d. Crystal structures of human CD1a, b, and d, as well as mouse CD1d, without loading specific antigens, ... when it was presented by heterologous human CD1d. Surprisingly, and unlike GSL antigens, borrelial α-GalDAG antigens can bind ... We show that CD1d binding of the borrelial α-GalDAG antigens is relatively promiscuous, in that it included some nonantigenic ...
more infohttps://www.pnas.org/content/107/4/1535?ijkey=ce0654cab5f74f3f02545c923aaa251074a37f5f&keytype2=tf_ipsecsha

Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells  | Journal of Experimental...Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells | Journal of Experimental...

The types of lipids loaded initially onto CD1d could affect the ability of the CD1d antigen to be edited by saposins or other ... also regulates CD1d presentation of glycolipid antigens in the liver and intestine. We show MTP RNA and protein in antigen- ... Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells Stephanie K. Dougan ... Tail-deleted forms of CD1d that fail to traffic to endosomes activate Vα14− NK1.1− NKT cells but cannot present antigen to ...
more infohttps://rupress.org/jem/article/202/4/529/53006/Microsomal-triglyceride-transfer-protein

Antigen-presenting glycoprotein CD1dAntigen-presenting glycoprotein CD1d

Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T- ... The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. ...
more infohttps://pharos.nih.gov/idg/targets/CD1D

The actin cytoskeleton modulates the activation of invariant NKT cells by segregating CD1d nanoclusters on antigen presenting...The actin cytoskeleton modulates the activation of invariant NKT cells by segregating CD1d nanoclusters on antigen presenting...

The actin cytoskeleton modulates the activation of invariant NKT cells by segregating CD1d nanoclusters on antigen presenting ... The actin cytoskeleton modulates the activation of invariant NKT cells by segregating CD1d nanoclusters on antigen presenting ...
more infohttps://www.imm.ox.ac.uk/publications/597636

Epigenetic regulation of CD1d-mediated antigen presentation in B cell lymphoma | Journal for ImmunoTherapy of Cancer | Full TextEpigenetic regulation of CD1d-mediated antigen presentation in B cell lymphoma | Journal for ImmunoTherapy of Cancer | Full Text

CD1d, a non-polymorphic MHC class I-like molecule, presents lipid antigens to Natural killer T (NKT) cells, which have potent ... Here we sought to test the hypothesis that B cell lymphomas use epigenetic mechanisms to dysregulate CD1d-mediated antigen ... These data indicate that HDACi differentially modulate CD1d and MHC class II-mediated antigen presentation and suggests a role ... resulted in a dose-dependent increase in CD1d-mediated NKT cell activation by lymphoma cells without altering CD1d or co- ...
more infohttps://jitc.biomedcentral.com/articles/10.1186/2051-1426-2-S3-P177

A Molecular Basis for the Exquisite CD1d-Restricted Antigen Specificity and Functional Responses of Natural Killer T Cells -...A Molecular Basis for the Exquisite CD1d-Restricted Antigen Specificity and Functional Responses of Natural Killer T Cells -...

A Molecular Basis for the Exquisite CD1d-Restricted Antigen Specificity and Functional Responses of Natural Killer T Cells ...
more infohttps://findanexpert.unimelb.edu.au/display/publication159664

The MHC class-I like molecule CD1d presents glycolipid antigens and thereby  |  Targeting the Hypoxia-Sensing PathwayThe MHC class-I like molecule CD1d presents glycolipid antigens and thereby | Targeting the Hypoxia-Sensing Pathway

The MHC class-I like molecule CD1d presents glycolipid antigens and thereby. By Abigail Sims , Published December 14, 2017 ... The MHC class-I like molecule CD1d presents glycolipid antigens and thereby activates invariant natural killer-T (NKT) cells. ... disc38 differentially regulate Compact disc1n proteins localization in THP-1 cells Since Compact disc1n is certainly an antigen ...
more infohttp://cloudlegalproject.org/the-mhc-class-i-like-molecule-cd1d-presents-glycolipid-antigens-and-thereby/

The actin cytoskeleton modulates the activation of iNKT cells by segregating CD1d nanoclusters on antigen-presenting cells. -...The actin cytoskeleton modulates the activation of iNKT cells by segregating CD1d nanoclusters on antigen-presenting cells. -...

Here, we show that the spatiotemporal distribution of CD1d molecules on the surface of antigen-presenting cells (APCs) ... autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d ... By using superresolution microscopy, we show that CD1d molecules form nanoclusters at the cell surface of APCs, and their size ... Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton ...
more infohttps://pharm.ox.ac.uk/publications/597636

CD1D | Cancer Genetics WebCD1D | Cancer Genetics Web

... cell antigen when presented on CD1d molecules expressed on professional antigen-presenting cells. Although CD1d-expressing ... CD1D is implicated in:. - antigen processing and presentation, endogenous lipid antigen via MHC class Ib - beta-2-microglobulin ... The frequency of CD1d(+)/CD19(+) cells, CD1d staining intensity and CD1d transcript levels increased with the disease stage. ... Through the analysis of CD1d expression by flow cytometry and qRT-PCR we showed lower CD1d molecule and CD1d mRNA expression in ...
more infohttp://www.cancerindex.org/geneweb/CD1D.htm

CD1d protein structure determines species-selective antigenicity of isoglobotrihexosylceramide (iGb3) to invariant NKT cells.CD1d protein structure determines species-selective antigenicity of isoglobotrihexosylceramide (iGb3) to invariant NKT cells.

... has been identified as a potent CD1d-presented self-antigen for mouse invariant natural killer T (iNKT) cells. The role of iGb3 ... Antigen Presentation. Antigens, CD1d / chemistry, immunology*, metabolism. Globosides / immunology*, metabolism. Humans. ... 0/Amino Acids; 0/Antigens, CD1d; 0/Globosides; 0/Receptors, Antigen, T-Cell; 0/Trihexosylceramides; 0/ ... Isoglobotrihexosylceramide (iGb3) has been identified as a potent CD1d-presented self-antigen for mouse invariant natural ...
more infohttp://www.biomedsearch.com/nih/CD1d-protein-structure-determines-species/23280365.html

RCSB PDB 









for 4F7ERCSB PDB for 4F7E

Crystal Structures of Bovine CD1d Reveal Altered αGalCer Presentation and a Restricted A Pocket Unable to Bind Long-Chain ... CD1D antigen, d polypeptide A 283 Bos taurus Fragment: UNP residues 129-405 Gene Name(s): CD1D Gene View ... Crystal structure of bovine CD1d with bound C16:0-alpha-galactosyl ceramide. *DOI: 10.2210/pdb4f7e/pdb ...
more infohttp://www.rcsb.org/pdb/explore/webMol.do?structureId=4F7E

RCSB PDB 









- 4F7E: Crystal structure of bovine CD1d with bound C16:0-alpha-galactosyl ceramide Macromolecule...RCSB PDB - 4F7E: Crystal structure of bovine CD1d with bound C16:0-alpha-galactosyl ceramide Macromolecule...

Crystal Structures of Bovine CD1d Reveal Altered αGalCer Presentation and a Restricted A Pocket Unable to Bind Long-Chain ... Antigen Processing and Presentation of Peptide Antigen Via Mhc Class I * Antigen Processing and Presentation of Exogenous ... Antigen Processing and Presentation of Endogenous Peptide Antigen Via Mhc Class I ... Crystal structure of bovine CD1d with bound C16:0-alpha-galactosyl ceramide. ...
more infohttp://www.rcsb.org/pdb/explore/derivedData.do?structureId=4F7E

The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function | JEMThe Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function | JEM

Indeed, the activation of iNKT cells requires TCR recognition of a glycolipid antigens-CD1d complex on the surface of APCs (1 ... iNKT cells recognize glycolipid antigens, such as α-galactosylceramide (α-GalCer), presented in the context of CD1d molecules ( ... and anti-NK1.1 mAbs and α-GalCer-loaded CD1d tetramers. Maturation of iNKT cells (CD1d tetramer+, CD3+, and CD8−) was assessed ... and CD1d tetramers (ProImmune). For lipid loading, CD1d tetramers were incubated overnight with a 12 molar excess of α-GalCer ( ...
more infohttp://jem.rupress.org/content/206/4/735

CD1d1 molecule ELISA Kits | Biocompare.comCD1d1 molecule ELISA Kits | Biocompare.com

The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool for detecting and quantifying antigens ... Human Antigen-presenting glycoprotein CD1d, CD1D ELISA Kit *. Detection Target: CD1d molecule ...
more infohttps://www.biocompare.com/pfu/110627/soids/2-1276981/ELISA_Kit/ELISA_CD1d1_molecule

Cytokine production by GD3-reactive NKTs. Mice were imm | Open-iCytokine production by GD3-reactive NKTs. Mice were imm | Open-i

Antigen-Presenting Cells/physiology. *Antigens, CD1/physiology. *Antigens, CD1d. *Cytokines/biosynthesis. *Female ... They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before ... They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before ... 2000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. GD3-reactive NKT cells did not react with GM2, a closely ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2196074_20030446f8&req=4

The expression of CD1d and GD2 on neuroblastoma (NB) ce | Open-iThe expression of CD1d and GD2 on neuroblastoma (NB) ce | Open-i

a) The surface CD1d expression levels of various NB cell lines are shown. (b) The CD1d express ... The expression of CD1d and GD2 on neuroblastoma (NB) cell lines. ( ... a) The surface CD1d expression levels of various NB cell lines are shown. (b) The CD1d expression levels of cell lines from ... a) The surface CD1d expression levels of various NB cell lines are shown. (b) The CD1d expression levels of cell lines from ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC4814252_CAS-107-233-g001&req=4

Similar articles for PubMed (Select 22319442) - PubMed - NCBISimilar articles for PubMed (Select 22319442) - PubMed - NCBI

Herpes Simplex Virus 1 Specifically Targets Human CD1d Antigen Presentation To Enhance Its Pathogenicity. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=22319442

Genatlas sheetGenatlas sheet

cell differentiation antigen CD1D, identified by monoclonal antibody NOR3, (see [email protected]). * HMC class I antigen-like glycoprotein ... is a CD1D receptor that inhibits CD1D-mediated immune responses (interaction between LILRB12 and CD1D may provide new insights ... binds to CD1D and inhibits its recognition by NKT cells * up-regulation of CD1C enhances NKT recognition of CD1D and down- ... CD1A, CD1B, CD1C, CD1D bind and present lipid-based antigens to T cells ...
more infohttp://genatlas.medecine.univ-paris5.fr/fiche.php?symbol=CD1D

The AMEDEO Literature GuideThe AMEDEO Literature Guide

Herpes simplex virus-1 specifically targets human CD1d antigen presentation to enhance its pathogenicity.. J Virol. 2018 Sep 5 ...
more infohttps://amedeo.com/medicine/hrp/jvirol.htm

Proteins matched: G3DSA:3.30.500.10 (G3DSA:3.30.500.10) | InterPro | EMBL-EBIProteins matched: G3DSA:3.30.500.10 (G3DSA:3.30.500.10) | InterPro | EMBL-EBI

Antigen-presenting glycoprotein CD1d. Ovis aries (Sheep). Loading... P01889 3D HLA class I histocompatibility antigen, B-7 ... H-2 class I histocompatibility antigen, L-D alpha chain. Mus musculus (Mouse). Loading... ... H-2 class I histocompatibility antigen, D-B alpha chain. Mus musculus (Mouse). Loading... ... Putative HLA class I histocompatibility antigen, alpha chain H. Homo sapiens (Human). Loading... ...
more infohttp://www.ebi.ac.uk/interpro/ISignatureProteins?sig=G3DSA:3.30.500.10&query=X
  • CD1d was expressed as a mature glycoprotein by these cells, and unlike the other members of the human CD1 family its expression was constitutive and was not strongly up-regulated by GM-CSF and IL-4 or a range of other cytokines. (nih.gov)
  • Humans express five family members (CD1a-e) that can be grouped into three groups based on sequence similarity: group 1 (CD1a-c), group 2 (CD1d), and group 3 (CD1e) ( 5 , 6 ). (pnas.org)
  • Crystal structures of human CD1a, b, and d, as well as mouse CD1d, without loading specific antigens, or in complex with different glycolipids or lipopeptides, have been extensively reviewed elsewhere ( 7 ⇓ ⇓ - 10 ). (pnas.org)
  • The development of MHC multimer technology has provided a breakthrough in the ability to follow T cell populations defined by their antigen specificity ( 28 )( 29 ). (rupress.org)
  • Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. (rupress.org)
  • CD1d-dependent NK T cells are believed to be involved in the regulation of immune responses as a result of their potent ability to secrete cytokines. (rupress.org)
  • Mice express only CD1d. (pnas.org)
  • GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of approximately 1:2000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. (nih.gov)
  • Recently, a different category of glycolipids, α-galactosyl diacylglycerolipids (α-GalDAG), have been identified as novel iNKT cell antigens. (pnas.org)
  • Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton and correlates with enhanced iNKT cell activation. (ox.ac.uk)
  • Overall, these results define a previously unidentified mechanism that modulates iNKT cell autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d nanoclusters. (ox.ac.uk)
  • Given the importance of human immune responses, we conducted a human-mouse cross-species analysis of iNKT-cell activation by iGb3-CD1d. (biomedsearch.com)
  • Here we show that human and mouse iNKT cells were both able to recognise iGb3 presented by mouse CD1d (mCD1d), but not human CD1d (hCD1d), as iGb3-hCD1d was unable to support cognate interactions with the iNKT-cell TCRs tested in this study. (biomedsearch.com)
  • In conclusion, our data indicate that iGb3 is unlikely to be a major antigen in human iNKT-cell biology. (biomedsearch.com)
  • Currently, the natural ligand(s) for CD1d-restricted NK T cells is unknown, although phosphoinositol-containing compounds have been suggested to be natural ligands for some of these cells ( 13 )( 14 )( 15 ). (rupress.org)
  • In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo . (pnas.org)
  • Invariant natural killer T cells (iNKT cells) respond to CD1d-presented glycolipids from Borrelia burgdorferi , the causative agent of Lyme disease. (pnas.org)
  • CD1d also can bind nonantigenic lipids, however, but unexpectedly, mouse CD1d orients the two aliphatic chains of a nonantigenic lipid rotated 180°, causing a dramatic repositioning of the exposed sugar. (pnas.org)
  • Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells. (nih.gov)
  • Despite their remarkably low surface expression of CD1d, all myeloid lineage cells tested were extremely potent APC for responses of NK T cell clones to the synthetic glycolipid antigen, alpha-galactosyl ceramide. (nih.gov)
  • Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. (jove.com)
  • Type I NKT cells are reactive to the marine sponge-derived glycolipid α-galactosylceramide (α-GalCer) ( 8 ), which forms a stable α-GalCer/CD1d tetramer reagent that can be used for detection of type I NKT cells ( 9 , 10 ). (frontiersin.org)
  • CD1d-dependent NK T cells also might be involved in some circumstances in the prevention of tumor metastases ( 9 ) and the response to some infectious agents ( 10 )( 11 )( 12 )( 13 ). (rupress.org)
  • Many hematologic malignancies express CD1d and the co-stimulatory proteins needed to induce anti-tumor responses by NKT cells, yet most tumors are poorly immunogenic. (biomedcentral.com)
  • Melanoma Dextramer collection 1 - comprises MHC Dextramers specific for 6 different melanoma-associated antigens and can be used for the detection, enumeration and isolation of melanoma-specific CD8+ T cells from blood or tumor tissue. (wikipedia.org)
  • Here we show that the mouse and human CD1d present glycolipids having different fatty acids, based in part upon a difference at a single amino acid position that is involved in positioning the sugar epitope. (pnas.org)
  • T cells recognize a diverse range of potential antigens through their highly polymorphic T cell receptor (TCR). (pnas.org)
  • CD1d is also known as R3G1 Some of the known ligands for CD1d are: α-galactosylceramide (α-GalCer), a compound originally derived from the marine sponge Agelas mauritanius with no physiological role but great research utility. (wikipedia.org)
  • Prominent localization of CD1d to the endocytic system of monocyte lineage cells was observed, and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. (nih.gov)
  • In contrast, type II NKT cells are not reactive to α-GalCer ( 11 , 12 ), instead they are thought to make up an oligoclonal population that recognizes a diverse repertoire of lipid antigens ( 5 , 7 , 13 ). (frontiersin.org)
  • In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of myeloid origin, including circulating monocytes, monocyte-derived dendritic cells and macrophages. (nih.gov)
  • Although mouse and human iNKT cells respond to different antigens based on subtle differences in their fatty acids, the mechanism by which fatty acid structure determines antigenic potency is not well understood. (pnas.org)
  • To assess the functional outcomes of epigenetic modulation, murine and human B cell lymphomas were pretreated with HDAC inhibitors and then we assessed their ability to process and present antigen. (biomedcentral.com)
  • These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids. (sciencemag.org)
  • As antibodies are designed to specifically recognize and eliminate invading antigens, they are effective weapons used by the immune system to combat infection. (pnas.org)
  • A large number of immunotherapies, currently in development, seek to induce, expand, activate or eliminate antigen-specific T cells. (wikipedia.org)