Substances that are recognized by the immune system and induce an immune reaction.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Substances elaborated by bacteria that have antigenic activity.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
Substances elaborated by viruses that have antigenic activity.
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary thymocytes, granulocytes, macrophages, erythrocytes, and fibroblasts. CD44 antigens are the principle cell surface receptors for hyaluronate and this interaction mediates binding of lymphocytes to high endothelial venules. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.
Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
Antibodies produced by a single clone of cells.
The 140 kDa isoform of NCAM (neural cell adhesion molecule) containing a transmembrane domain and short cytoplasmic tail. It is expressed by all lymphocytes mediating non-MHC restricted cytotoxicity and is present on some neural tissues and tumors.
Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.
Surface antigens expressed on myeloid cells of the granulocyte-monocyte-histiocyte series during differentiation. Analysis of their reactivity in normal and malignant myelomonocytic cells is useful in identifying and classifying human leukemias and lymphomas.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Tetraspanin proteins found at high levels in cells of the lymphoid-myeloid lineage. CD53 antigens may be involved regulating the differentiation of T-LYMPHOCYTES and the activation of B-LYMPHOCYTES.
A cell adhesion protein that was originally identified as a heat stable antigen in mice. It is involved in METASTASIS and is highly expressed in many NEOPLASMS.
Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Substances of fungal origin that have antigenic activity.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The major group of transplantation antigens in the mouse.
A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.
Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Glycoproteins found on the membrane or surface of cells.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Sites on an antigen that interact with specific antibodies.
A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.
A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.
Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.
Established cell cultures that have the potential to propagate indefinitely.
A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES.
Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Oligosaccharide antigenic determinants found principally on NK cells and T-cells. Their role in the immune response is poorly understood.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds to CD27 ANTIGEN. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS where it plays a role in stimulating the proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
Glycoproteins with a wide distribution on hematopoietic and non-hematopoietic cells and strongly expressed on macrophages. CD58 mediates cell adhesion by binding to CD2; (ANTIGENS, CD2); and this enhances antigen-specific T-cell activation.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Progenitor cells from which all blood cells derive.
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
Tetraspanin proteins that are involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Proteins prepared by recombinant DNA technology.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.
Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.
Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.
A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.
An encapsulated lymphatic organ through which venous blood filters.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.
A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A class of enzymes involved in the hydrolysis of the N-glycosidic bond of nitrogen-linked sugars.
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
A widely distributed cell surface transmembrane glycoprotein that stimulates the synthesis of MATRIX METALLOPROTEINASES. It is found at high levels on the surface of malignant NEOPLASMS and may play a role as a mediator of malignant cell behavior.
A general term for various neoplastic diseases of the lymphoid tissue.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.
An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A widely expressed transmembrane glycoprotein that functions as a METASTASIS suppressor protein. It is underexpressed in a variety of human NEOPLASMS.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A cell line derived from cultured tumor cells.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.
A cell adhesion molecule of the immunoglobulin superfamily that is expressed in ENDOTHELIAL CELLS and is involved in INTERCELLULAR JUNCTIONS.
Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Antibodies obtained from a single clone of cells grown in mice or rats.
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
A heterodimeric protein that is a cell surface antigen associated with lymphocyte activation. The initial characterization of this protein revealed one identifiable heavy chain (ANTIGENS, CD98 HEAVY CHAIN) and an indeterminate smaller light chain. It is now known that a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS) can dimerize with the heavy chain. Depending upon its light chain composition a diverse array of functions can be found for this protein. Functions include: type L amino acid transport, type y+L amino acid transport and regulation of cellular fusion.
The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
The sum of the weight of all the atoms in a molecule.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.
Immunoglobulins produced in response to VIRAL ANTIGENS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
A glycolipid, cross-species antigen that induces production of antisheep hemolysin. It is present on the tissue cells of many species but absent in humans. It is found in many infectious agents.
Elements of limited time intervals, contributing to particular results or situations.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).

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)

CD1d-restricted natural killer T (NKT) cells are growing as essential regulators of the immune system response to infectious agents, including infection; (ii) service of NKT cells requires acidification-dependent handling of glycolipid antigens within the endolysosomal compartment; and (iii) endolysosomal acidification may become reduced in CF. growing mainly because essential regulators of the immune system response to infectious providers.5,6 The NKT cells may be particularly important in CF as evidence suggests that NKT cells play a central role in clearing from the GDC-0449 lung7 and gastrointestinal tract.8 In contrast to conventional major histocompatibility complex-restricted Capital t cells, NKT cells express a semi-invariant T-cell receptor (iTCR) that recognizes glycolipid antigens presented by CD1m substances on the surface of antigen-presenting cells, such as DCs and macrophages.5,9 Current knowledge of the glycolipid antigens that activate NKT cells for antimicrobial defence is ...
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 ...
Natural Killer T (NKT) cells are lipid-reactive CD1d-restricted T lymphocytes important in infection cancer and autoimmunity. and self lipid antigen induction for NKT cells. Intro Natural killer T (NKT) cells are XL-888 a subpopulation of unconventional T lymphocytes that communicate a restricted T cell receptor (TCR) repertoire and several molecules characteristic for NK cells (Bendelac et al. 2007 Kronenberg 2005 Following activation NKT cells respond by a rapid burst of cytokines secreting primarily interferon-γ(IFN-γ) and interleukin-4 (IL-4) therefore regulating the quality of downstream immune reactions (Bendelac et al. 2007 Consequently NKT cells play a role in various disease conditions including infections (Tupin et al. 2007 malignancy (Cui et al. 1997 Dhodapkar 2009 and autoimmunity (Shi and Vehicle Kaer 2006 such as diabetes (Hong et al. 2001 Sharif et al. 2001 and multiple sclerosis (Miyamoto et al. 2001 NKT cells identify lipid antigens primarily belonging to the group of ...
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
NKT cells have a central role in immune responses ranging from tumor rejection to the regulation of autoimmunity. Although they are believed to be present in most strains of mice, the identification of these cells in mice lacking NK1.1 expression has been difficult. A range of surrogate phenotypes has been used in an attempt to identify NKT cells in all strains of mice; however, the effectiveness of these phenotypes in isolating these cells remains uncertain. Thus, if we are to interpret studies of NKT cells in strains other than C57BL/6 with confidence, it is important to verify the status of NKT cells in these strains with reliable markers. The marker of choice for NKT cells has traditionally been the NK1.1 molecule, used in conjunction with αβTCR, CD4, and CD8 labeling. The generation of BALB/c and NOD mice congenic for the NK1.1 locus has made it possible to compare and contrast NK1.1+ T cells between these strains. NK1.1+ T cells were indeed present in each strain and, with the exception ...
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 ...
A subset of CD161 (NK1) T cells express an invariant Vα14Jα281TCR-α chain (Vαinvt T cells) and produce Th2 and Th1cytokines rapidly in response to CD1d, but their physiological function(s) remain unclear. We have found that CD1d-reactive T cells mediate to resistance against the acute, cytopathic virus diabetogenic encephalomyocarditis virus (EMCV-D) in relatively Th1-biased,C57BL/6-based backgrounds. We show now that these results generalize toTh2-biased, hypersensitive BALB/c mice. CD1d-KO BALB/c mice were more susceptible to EMCV-D. Furthermore, α-galactosylceramide(α-GalCer), a CD1d-presented lipid antigen that specifically activates Vαinvt T cells, protected wild-type (WT) mice against EMCV-D-induced encephalitis, myocarditis, and diabetes. In contrast, neither CD1d-KO nor Jα281-KO mice were protected byα-GalCer. Finally, disease in Jα281-KO mice was comparable to WT,indicating for the first time equivalent roles for CD1d-reactiveVαinvt and noninvariant T cells in resistance to acute
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.
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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 ...
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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 ...
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 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
In experimental crescentic GN, immature kidney DCs are protective13 until they mature, when inflammation becomes chronic.12 The underlying mechanisms remain to be elucidated. We speculated that, in this early phase, DCs might suppress harmful immune responses by recruiting anti-inflammatory leukocytes, and we addressed this hypothesis in NTN, a model of crescentic GN. When we depleted DCs in CD11c.LuciDTRmice with NTN, we noted that iNKT cells but not proinflammatory leukocytes were markedly reduced within the kidney. This finding sparked our interest, because two recent studies had shown a protective role for NKT cells in renal inflammation. Anti-GBM GN was aggravated in NKT cell-deficient CD1d knockout mice, and adoptively transferred NKT cells localized to the inflamed kidney and prevented this phenotype, which was astonishing, because NKT cells cannot recognize antigen in CD1d-deficient mice.18 Nevertheless, Mesnard et al.19 performed this experiment 1 year later in Jα18 knockout mice, ...
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, ...
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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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Human Vα24− CD1d-restricted T cells use variation in their CDR1α loop to respond to lipid antigens presented by CD1d, altering their specificities from that of invariant natural killer T cells.
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 ...
Plasmalogen lysophosphatidylethanolamine (pLPE) had been identified as a self antigen for natural killer T cells (NKT cells). It is very important in the development, maturation and activation of NKT cells in thymus. Besides, pLPE is a novel type of antigen for NKT cells. To evaluate the structure-activity relationship (SAR) of this new antigen, pLPE and its analogues referred to different aliphatic chains and linkages at the sn-1 position of the glycerol backbone were synthesized, and the biological activities of these analogues was characterized. It is discovered that the linkages between phosphate and lipid moiety are not important for the antigens activities. The pLPE analogues 1, 3, 4, 7 and 9, which have additional double bonds on lipid parts, were identified as new NKT agonists. Moreover, the analogues 4, 7 and 9 were discovered as potent Th2 activators for NKT cells ...
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
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 ...
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in International Immunology following peer review. The definitive publisher-authenticated version International Immunology is available online at: ...
NKT cells are potent regulatory T cells that prevent the development of several autoimmune diseases. Analysis of NKT cell regulatory function in the NOD mouse has revealed that NKT cells inhibit the development of type 1 diabetes by impairing the differentiation of anti-islet T cells into Th1 effector cells. In the present study, we have performed in vitro and in vivo experiments to determine the respective role of cytokines and cell contacts in the blockade of T cell differentiation by NKT cells. These experiments reveal that cytokines such as IL-4, IL-10, IL-13, and TGF-beta, that have been involved in other functions of NKT cells, play only a minor role if any in the blockade of T cell differentiation by NKT cells. Diabetes is still prevented by NKT cells in the absence of functional IL-4, IL-10, IL-13, and TGF-beta. In contrast, we show for the first time that cell contacts are crucial for the immunoregulatory function of NKT cells.
Vα24-invariant natural killer T cells (NKTs) localize to tumors and have inherent antitumor properties, making them attractive chimeric antigen receptor (CAR) carriers for redirected cancer immunotherapy. However, clinical application of CAR-NKTs has been impeded, as mechanisms responsible for NKT expansion and the in vivo persistence of these cells are unknown. Here, we demonstrated that antigen-induced expansion of primary NKTs in vitro associates with the accumulation of a CD62L+ subset and exhaustion of CD62L- cells. Only CD62L+ NKTs survived and proliferated in response to secondary stimulation. When transferred to immune-deficient NSG mice, CD62L+ NKTs persisted 5 times longer than CD62L- NKTs. Moreover, CD62L+ cells transduced with a CD19-specific CAR achieved sustained tumor regression in a B cell lymphoma model. Proliferating CD62L+ cells downregulated or maintained CD62L expression when activated via T cell receptor alone or in combination with costimulatory receptors. We generated ...
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. ^
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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. ...
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Authors: Hamish EG McWilliam, Sidonia BG Eckle, Alex Theodossis, Ligong Liu, Zhenjun Chen, Jacinta M Wubben, David P Fairlie, Richard A Strugnell, Justine D Mintern, James McCluskey, Jamie Rossjohn, Jose A Villadangos
Scientists have shown that SARS-CoV-2 can make itself unrecognizable to the killer T cells of the immune response through mutations. The findings of the research provide important information for the further development of vaccines.
The researchers goal was to create a therapy that would permanently boost the bodys ability to naturally produce more iNKT cells.
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: Sarcoidosis is a multisystem disorder that predominantly involves the lungs, characterised by a T-helper 1 (Th1) biased CD4-positive T-cell response and granuloma formation, for which the explanation is unknown. A newly identified subset of T-cells with immunoregulatory functions, CD1d-restricted natural-killer T (NKT) cells, has been shown to protect against disorders with increased CD4-positive Th1 responses in animals. We explored whether abnormalities in these cells are implicated in the pathogenesis of sarcoidosis. METHODS: We generated fluorescence-labelled CD1d-tetrameric complexes and used them, with monoclonal antibodies to Valpha24 and Vbeta11 T-cell receptor, to assess the frequency of CD1d-restricted NKT cells in the peripheral blood of 60 patients with histologically proven sarcoidosis (16 with Lofgrens syndrome) and 60 healthy controls. Lung lymphocytes were also analysed in 16 of the patients with sarcoidosis. FINDINGS: CD1d-restricted NKT cells were absent or greatly reduced
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 T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Valpha24/Vbeta11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls. Unlike Valpha24/Vbeta11 NKT cells found in blood, those in the liver appeared to be recently activated.
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.
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 ..
Background Compact disc1d is a nonpolymorphic MHC course I-like molecule which presents nonpeptide ligands e. design and amount of Compact disc1d appearance for hematopoieitic cells of both types. Notable can be the recognition of Compact disc1d proteins in mouse and rat Paneth cells aswell as the incredibly high Compact disc1d appearance in acinar exocrine cells from the rat pancreas as well as the appearance of Compact disc4 on rat marginal area B cells. Both mAbs blocked α-galactosylceramide recognition by major mouse and rat NKT cells. Oddly enough both mAbs differed within their effect on the activation of varied autoreactive T cell hybridomas like the XV19.2 hybridoma whose activation was improved with the WTH-1 mAb. Conclusions/Significance Both book monoclonal antibodies referred to in this research allowed the evaluation of Compact disc1d appearance and Compact disc1d-restricted T cell replies in the rat for the very first time. They provided new insights into mechanisms of ...
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 ...
The human MHC class I-like molecule CD1b is distinctive among CD1 alleles in that it is capable of presenting a set of glycolipid species that show a very broad range of variation in the lengths of their acyl chains. A structure of CD1b complexed with relatively short acyl chain glycolipids plus detergent suggested how an interlinked network of channels within the Ag-binding groove could accommodate acyl chain lengths of up to 80 carbons. The structure of CD1b complexed with glucose monomycolate, reported in this study, confirms this hypothesis and illustrates how the distinctive substituents of intracellular bacterial glycolipids can be accommodated. The Ag-binding groove of CD1b is, uniquely among CD1 alleles, partitioned into channels suitable for the compact accommodation of lengthy acyl chains. The current crystal structure illustrates for the first time the binding of a natural bacterial lipid Ag to CD1b and shows how its novel structural features fit this molecule for its role in the immune
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NK1.1neg iNKT cells are the major iNKT subset producing IL-17. Liver MNCs from wild-type mice were stained with CD1d/α-GalCer tetramers, anti-TCRβ, and NK1.1 before sorting. (A) Representative FACS profiles obtained before (left) and after (right) sorting of CD1d/α-GalCer tetramers +NK1.1neg (NK1.1neg iNKT) and CD1d/α-GalCer tetramers +NK1.1pos (NK1.1pos iNKT) liver iNKT cells. (B-F) Sorted NK1.1neg iNKT and NK1.1pos iNKT liver MNCs were stimulated with α-GalCer (B-D) or synthetic B. burgdorferi glycolipids (BbGL-II [IIc]) or GalA-GSL (GSL; E and F) plus irradiated liver MNCs from Jα18−/− mice as APCs. Sorted CD4+CD62L+ T cells from Jα18−/− mice were stimulated with α-GalCer plus irradiated liver MNCs from Jα18−/− mice as APCs (G). 3 d later, IL-17 (B, E, and G), IL-4 (C and F), and IFN-γ (D) were measured in the supernatants. No cytokine was detected in the absence of α-GalCer stimulation, in the absence of APCs or when APCs alone were stimulated with α-GalCer (not ...
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 ...
Invariant human TCR Valpha24-Jalpha18+/Vbeta11+ NKT cells (iNKT) are restricted by CD1d-alpha-glycosylceramides. We analyzed crystal structures and binding characteristics for an iNKT TCR plus two CD1d-alpha-GalCer-specific Vbeta11+ TCRs that use different TCR Valpha chains. The results were similar to those previously reported for MHC-peptide-specific TCRs, illustrating the versatility of the TCR platform. Docking TCR and CD1d-alpha-GalCer structures provided plausible insights into their interaction. The model supports a diagonal orientation of TCR on CD1d and suggests that complementarity determining region (CDR)3alpha, CDR3beta, and CDR1beta interact with ligands presented by CD1d, whereas CDR2beta binds to the CD1d alpha1 helix. This docking provides an explanation for the dominant usage of Vbeta11 and Vbeta8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d-alpha-GalCer.
At the functional level, rat splenocytes and IHLs have been shown to secrete IFN-γ and IL-4 in response to stimulation with α-GalCer [12, 13] in a CD1d-dependent fashion ([13] and this study). α-GalCer-loaded mouse or human CD1d tetramers bind very poorly to the rat iNKT-TCR [12] (Monzon-Casanova, Herrmann, unpublished data). This is in contrast to the mouse and the human, both of which show CD1d/iNKT-TCR cross-species reactivity. [1], but it explains why a discrete population was not observed among rat IHLs using mouse CD1d tetramers [12]. Furthermore, former attempts to identify rat iNKT cells using surrogate markers have also failed as no cell population has yet been found with the features predicted for iNKT cells based on their mouse counterparts. Instead, rat NKR-P1A/B-positive SP600125 price T cells are found in the spleen and the liver at similar frequencies, show no BV8S2 or BV8S4 bias, produce IFN-γ but not IL-4, and most of them express CD8β [9, 12, 14-16]. In the present study, ...
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 ...
applicable for standard unlabeled Pentamers and ProVE® Pentamers). Biotin-labeled Pentamer staining protocol. Pentamer staining for whole blood. Staining a single cell sample with multiple labeled Pentamers. Staining a single cell sample with multiple unlabeled Pentamers. Pentamer immunohistochemistry protocol. ...
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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 ...
... 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 ...
"Glycolipid antigen processing for presentation by CD1d molecules". Science. 291 (5504): 664-667. doi:10.1126/science.291.5504. ... which is the MHC class I molecule that presents lipid antigens. He has led the field in defining microbial antigens from ... Kronenberg's work had a major impact in defining how glycolipid antigens are taken into cells and processed in lysosomes and ... the Thymus Leukemia antigen. His work has determined how the balance of regulatory versus pro-inflammatory responses occurs, ...
... and a model CD1d antigen. The invariant T cell receptor of the iNKT cell is able to bind the CD1d:glycolipid complex leading to ... In combination with a peptide antigen, α-GalCer is able to stimulate a strong immune response against the epitope. The CD1d: ... Godfrey, Dale I.; Kronenberg, Mitchell (2004-11-15). "Going both ways: Immune regulation via CD1d-dependent NKT cells". Journal ...
... 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 ...
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, ... NKT cells recognize protected microbial lipid agents which are presented by CD1d-expressing antigen presenting cells. This ...
Both foreign and endogenous lipid antigens activate these cells. The TCR usually recognizes the hydrophilic part of the antigen ... Natural killer T (NKT) cells are a similar population with affinity to CD1d (the only group 2 CD1 molecule). Both groups ... Small hydrophobic antigens lacking a polar part have also been shown to activate CD1a-restricted T cells, indicating that in ... Most of these antigens are bound to CD1b. Group 1 CD1-restricted T cells are activated after Mycobacterium infection and ...
Thus, type II NKT cells seem to recognize diverse antigens presented by CD1d and given that these cells seem to be more ... phospholipid antigen lysophosphatidylcholine and some other phospholipid, and lysophospholipid antigens, including ... CD1d-restricted NKT cells are divided into 2 groups. Type I NKT cells are also called 'invariant NKT cells' or 'iNKT cells', ... CD1d-restricted NKT cells contribute to host defence by influencing the function of macrophages, dentritic cells, B cells and ...
Alkyl components of antigens are attached in the hydrophobic groove and a hydrophilic part stands out from the CD1b molecule ... The human CD1 locus is found on chromosome 1 and contains five nonpolymorphic genes (CD1a, CD1b, CD1c, CD1d and CD1e). CD1b ... CD1b molecule has the largest antigen-binding cleft within the CD1 family. Whereas the microbial lipids tend to have longer ... Compared to other CD1 molecules this unique arrangement of CD1b provides the possibility of binding a wide spectrum of antigens ...
It has been identified as a CD1d- presented self-antigen for an innate type of immune cells termed as Natural Killer T (NKT) ...
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 ...
NKT cells recognize glycolipid antigens presented by CD1d. Once activated, these cells can perform functions ascribed to both ... Antigen-naive T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help. Antigen ... These self-antigens are expressed by thymic cortical epithelial cells on MHC molecules, which reside on the surface of cortical ...
The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell ... Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature 345:449-452. Moins- ... NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J ... The crystal structure of human CD1d with and without alpha-galactosylceramide. Nature Immunol 6:819-826. McCarthy, C., D. ...
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 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". The Journal of ... MTTP is also involved in the late stage of CD1d trafficking in the lysosomal compartment, ...
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 ...
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 ... by specialized white blood cells activate the adaptive immune system through antigen presentation act as a physical and ...
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 ... γδ T cells are believed to have a prominent role in recognition of lipid antigens. They are of an invariant nature and may be ... It is still not clear whether these non-peptidic antigens bind directly to the Vγ9/Vδ2 TCR or if a presenting element exists. ...
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 ...
... antigen without any need for antigen processing. Such antigens may be large molecules found on the surfaces of pathogens, but ... Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted natural killer T cells, γδ T cells ... antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are ... Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to ...
MZ B cells shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery to ... MZ B cells characteristically express high levels of CD1d, which is an MHC class I-like molecule involved in the presentation ... MZ B cells respond to a wide spectrum of T-independent, but also T-dependent antigens. It is believed that MZ B cells are ... Moreover, MZ B cells are potent antigen-presenting cells, that are able to activate CD4+ T cells more effectively than FO B ...
... 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 (October 2003). "Role of CD1d-restricted NKT cells in microbial immunity". Infection and Immunity. 71 (10): ... "Entrez Gene: HLA-G HLA-G histocompatibility antigen, class I, G". Attia JV, Dessens CE, van de Water R, Houvast RD, Kuppen PJ, ... McIntire RH, Hunt JS (April 2005). "Antigen presenting cells and HLA-G--a review". Placenta. 26 (Suppl A): S104-S109. doi: ...
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. ...
Ho, Ling-Pei (2004). The role of CD1d restricted NKT cells in the immunopathology of sarcoidosis (Thesis). Thesis DPhil-- ... "Nixon, Douglas". Makgoba, M. W. (1983). Studies on the polymorphism of HLA class II antigens (Thesis). Thesis DPhil--University ... Bowness, Paul (1993). Recognition of antigen and superantigen by cytotoxic lymphocytes (Thesis). Thesis DPhil--University of ... "Phenotypic analysis of antigen-specific T lymphocytes". Science. 274 (5284): 94-96. Bibcode:1996Sci...274...94A. doi:10.1126/ ...
... 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 ...
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 ...
Reduction of CD3 or CD1d may lead to dysfunction of T cells by deletion of ABCA7. On the other hand, transfected and expressed ... tandem linkage with the minor histocompatibility antigen HA-1 gene". Biochemical and Biophysical Research Communications. 278 ( ... January 2017). "ATP Binding Cassette Transporter ABCA7 Regulates NKT Cell Development and Function by Controlling CD1d ... January 2017). "ATP Binding Cassette Transporter ABCA7 Regulates NKT Cell Development and Function by Controlling CD1d ...
Crystal structure of bovine CD1d with bound C12-di-sulfatide ... CD1D antigen, d polypeptide: A. Beta-2-microglobulin: B. SMTL: ... Crystal structure of bovine CD1d with bound C12-di-sulfatide Coordinates. PDB Format Method. X-RAY DIFFRACTION 2.86 Å. Oligo ... Wang, J. et al., Crystal Structures of Bovine CD1d Reveal Altered αGalCer Presentation and a Restricted A Pocket Unable to ...
Structural analogues of α-GalCer have been synthesised to determine which components are required for CD1d pr … ... binds to CD1d and exhibits potent activity as a ligand for invariant CD1d-restricted natural killer-like T cells (iNKT cells). ... Antigen-Presenting Cells / drug effects * Antigen-Presenting Cells / immunology * Antigen-Presenting Cells / metabolism ... binds to CD1d and exhibits potent activity as a ligand for invariant CD1d-restricted natural killer-like T cells (iNKT cells). ...
T cells follow specific selection rules and are poised to recognize self or evolutionarily conserved microbial antigens. We ... Human and mouse type I natural killer T cell antigen receptors exhibit different fine specificities for CD1d-antigen complex. J ... CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448, 44-49 (2007). This paper provides the ... Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor. Nat. Immunol. 13, 857-863 (2012). ...
Antigen-presenting cells present antigen to the NKT cells via the major histocompatibility complex-like molecule CD1d. NKT ... Analysis of the secreted cytokine profile and of binding of alpha-galactosylceramide-loaded CD1d to NKT cells suggests that CD4 ... The evidence for an autoimmune etiology includes pathological findings of infiltrating T cells, the presence of antigen- ... antibody complexes in affected cartilage, cellular and humoral responses against collagen type II and other collagen antigens, ...
CD1d-mediated antigen presentation to natural killer T (NKT) cells. Crit Rev Immunol. 2003;23(5-6):403-419. ... NKT cells agonists presented by CD1d-expressing B-cells to NKT cells have been shown to induce NKT-cell anergy in mice.41 In ... GSLs from S. paucimobilis are CD1d-specific ligands for type I NKT cells.16 The combination of glycosphingosomes and Lip-Dox ... Gycolipid antigen induces long term natural killer T cell anergy in mice. J Clin Invest. 2005;115(9):2572-2583. ...
ACTIVATION-INDUCED EXPRESSION OF CD1D ANTIGEN ON MATURE T CELLS. JOURNAL OF LEUKOCYTE BIOLOGY; Lugar: Bethesda, MD; Año: 2001 ... The Tn antigen promotes lung tumor growth by fostering immunosuppression and angiogenesis via interaction with Macrophage ... Prognostic Value of the Interaction between Galectin-3 and Antigen Carbohydrate 125 in Acute Heart Failure ... TISSUE ANTIGENS; Lugar: Victoria, Australia; Año: 2004 vol. 64 p. 1 - 12 ...
Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with ... such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known immune checkpoint ... no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known ... dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homologue, ...
CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science. 1999 Jan 08; 283(5399):225- ... Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis ...
Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science, 303, 523-527. ...
Studying the evolution of mammalian CD1d presentation of lipid antigen to NK-T Cells. Currently Ph.D. Student in Genetics, ... Phylogeny of chimeric antigen receptors. B.S. Microbiology, Colorado State University, Ft. Collins CO. M.B.A. Colorado State ... Studying the immunogenetic plasticity of shark and cow lymphocyte antigen receptors. B.S. Biomedical Sciences, Texas A&M ...
Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are ... CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells ... Chaudhry MS, Karadimitris A, 2014, Role and Regulation of CD1d in Normal and Pathological B Cells, JOURNAL OF IMMUNOLOGY, Vol: ... CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells ...
CD1d expression is prerequisite for antigen-specific iNKT-cell activation (86). This molecule resembles those in the class-I ... Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments. J Exp Med 1999; ... The affinity of iNKT TCR for CD1d-bound antigens is not always enough to predict cytokine response types (Th1 or Th2). ... Several lipidic or glycolipidic antigens have been identified, which may be presented by CD1d and activate iNKT cells. KRN7000 ...
Since both HC and EC express CD1d on the cell surface (Figure 3A), both cell sets are able to present antigen to iNKT cells. We ... On the other hand, free αGalCer is taken up by CD1d-positive cells, with these cells presenting CD1d-αGalCer complex to iNKT ... may play a role in antigen presentation to iNKT cells; however, how other CD1d-positive cells participate in this reaction is ... CD1d-restricted and TCR-mediated activation od Vα14 NKT cells by glycosylceramides. Science 278: 1626-1629, 1997. ...
One possible explanation for this second wave of expansion is the priming of CD4+ T cells by antigen-specific B cells, but ... Innate T cells, including CD1d-restricted invariant natural killer T (iNKT) cells, are characterized by their rapid activation ... In SARS-1 survivors, antigen-specific memory T cells were detected up to 11 years after the initial infection, when viral- ... It was previously shown that TCRs recognising the same antigens frequently have highly similar TCR sequences (Dash et al., 2017 ...
... interactions of T cells and antigen-presenting cells can also be blocked by the MR1 antibody. ,/span>,span style=font-style: ... interactions of T cells and antigen-presenting cells can also be blocked by the MR1 antibody. ,/span>,span style=font-style: ... and disrupts antigen-specific T-cell responses.,/span> ... and disrupts antigen-specific T-cell responses.,/span> ... CD154 plays an important role in costimulatory interactions between T and B lymphocytes and between antigen-presenting cells ...
Activation of invariant CD1d-dependent NKT cells (iNKT cells) in vivo through administration of the glycolipid ligand α- ... This process enhances T cell immunity to antigens presented by the DC. The adjuvant activity is further amplified if APCs are ... Activation of invariant CD1d-dependent NKT cells (iNKT cells) in vivo through administration of the glycolipid ligand α- ... "Utilizing the Adjuvant Properties of CD1d-Dependent NK T Cells in T Cell-Mediated Immunotherapy." JOURNAL OF CLINICAL ...
Murine CD1d-restricted T cell recognition of cellular lipids. Jenny E. Gumperz, Christopher Roy, Anna Makowska, Deirdre Lum, ... Dive into the research topics of Murine CD1d-restricted T cell recognition of cellular lipids. Together they form a unique ...
Structure of the self-antigen iGb3 bound to mouse CD1d and in complex with the iNKT TCR. ... Structure of New Antigen Receptor variable domain from sharks. 1ves. Structure of New Antigen Receptor variable domain from ... Structure of new antigen receptor variable domain from sharks. 2ywz. Structure of new antigen receptor variable domain from ... Structure of the mouse CD1d-4ClPhC-alpha-GalCer-iNKT TCR complex. 4irs. Structure of the mouse CD1d-PyrC-alpha-GalCer-iNKT TCR ...
Antigen, CD1d. CD1d Antigen. CD1d Antigens. Cd1d Molecule. Tree number(s):. D23.050.301. D23.050.301.264. ... 2009; CD1D ANTIGEN (now ANTIGENS, CD1D) was indexed under ANTIGENS CD1 1999-2008. ... Antigens, CD1d Entry term(s). Antigen, CD1d CD1d Antigen CD1d Antigens Cd1d Molecule ... Antigens, CD1d - Preferred Concept UI. M0518843. Scope note. A major histocompatibility complex class I-like protein that ...
CD1d Restriction. Unlike classical T cells, NKT cells are activated by CD1d and not MHCs. While classical T cells recognize MHC ... NKT cells will reciprocally activate its antigen presenting cell upon lipid/glycolipid presentation. Once mature, NKT cells ...
The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. ... Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T- ... Download Data for CD1D. data still loading.... Description of the protein which includes the UniProt Function and the NCBI Gene ... Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T- ...
CD1d. int. Tim1. int. plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138. +. ... as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10- ...
Antigens, CD1d.immunology. CD4-Positive T-Lymphocytes.immunology. Glycolipids.immunology. HEK293 Cells. Humans. Mice. Mice, ... These data provide new insight into glycolipid antigen recognition by the immune system and indicate the existence of a ... Using model carbohydrate systems (isogloboside 3 and B blood group antigen), we examined the anti-carbohydrate response on ... these antibody responses were CD1d and NKT cell independent. They also did not require peptide help. ...
Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible ...
19.Faveeuw C,Angeli V, Fontaine J,Maliszewski C,Capron A,Van Kaer L,Moser M,Capron M,Trottein F.Antigen presentation by CD1d ... Hypersensitivity pneumonitis -Bird antigens -Actinomycetes Table 4: Pathologic Findings and Supportive Diagnostic Tests for ... Galactomannin (Aspergillus antigen). Bartonella sp.. Necrotizing liver granulomas. Serologies, Blood cultures held for 4 weeks ... Serologies, Urine antigen. Brucella sp.. Liver, spleen granulomas with central necrosis, peripheral fibrosis, bacilli. ...
Antígenos CD1d. Antigens, CD1d. Antígenos CD1d. Antígenos Embrionários Estágio-Específicos. Stage-Specific Embryonic Antigens. ...
Adipocytes could act as antigen presenting cells via. expression of key molecules for antigen presentation in obese adipose ... In addition, adipocytes could modulate the function and activation of iNKT cells via high expression of CD1d molecules in ... Model of adipocytes as antigen presenting cells. ...
We also report that schistosome egg-sensitized dendritic cells (DCs) activate, in a CD1d-dependent manner, iNKT cells to ... Finally, we propose that self, rather than parasite-derived, CD1d-restricted ligands are implicated in iNKT cell stimulation. ... Mouse CD1d-restricted NKT cells, including invariant (i)NKT cells, are innate cells activated by glycolipid Ags and play ... Animals, Antigens, CD1, Antigens, CD1d, Cells, Cultured, Dendritic Cells, Female, Killer Cells, Natural, Ligands, Lymphocyte ...
Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d- ... Imunidade Inata , Metabolismo dos Lipídeos , Antígenos CD1d/genética , Antígenos CD1d/metabolismo , Macrófagos/metabolismo , ... Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking ... Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function ...
  • Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. (
  • CD1d is a MHC-class-I-like molecule that mediates the presentation of lipid or glycolipid antigens to T cells. (
  • These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. (
  • Invariant natural killer T (iNKT) cells are characterized by the expression of an invariant T cell receptor α chain encoded by Vα14Jα18 in mice and Vα24Jα18 in humans and recognize numerous endogenous and exogenous glycolipids presented by the major histocompatibility complex class I-like CD1d molecule ( 1 , 2 ). (
  • Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. (
  • Of these molecules CD1d has been the subject of much interest over the past 10 years following the discovery that this molecule presents antigens to a group of T cells known as invariant natural killer T cells (iNKT). (
  • In addition to a compound known as an antigen which is specific to the tumor and reacts with a T-cell receptor when presented by dendritic cells (DCs), it also requires a co-stimulatory molecule that tumors appear to lack. (
  • Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. (
  • But CD1d is the only CD1 molecule has been found in mouse. (
  • His work focuses on many connections between Antibody and other disciplines, such as Cell adhesion molecule, that overlap with his field of interest in Mucin, Carcinoembryonic antigen, Function and Internal medicine. (
  • Here we determined that species-specific glycolipid activity was due to a lack of recognition of the analogues by the T-cell receptors on human iNKT cells rather than insufficient presentation of the analogues on human CD1d molecules. (
  • Activation of invariant CD1d-dependent NKT cells (iNKT cells) in vivo through administration of the glycolipid ligand α-galactosylceramide (α-GalCer) or the sphingosine-truncated α-GalCer analog OCH leads to CD40 signaling as well as the release of soluble molecules including type 1 and γ interferons that contribute to DC maturation. (
  • To elicit an anti-carbohydrate immune response, glycoproteins can be processed to glycopeptides and presented by the classical antigen-presenting molecules, major histocompatibility complex (MHC) Class I and II. (
  • Adipocytes could act as antigen presenting cells via expression of key molecules for antigen presentation in obese adipose tissue. (
  • The CD1 family of antigen-presenting molecules consists of five members, CD1a to e. (
  • Abstract :Natural killer T (NKT) cells are a population of T cells that share some characteristics with natural killer (NK) cells, which can recognize glycolipids presented by CD1d molecules expressed on antigen-presenting cells through cell recognition pathway. (
  • Data_Sheet_1.pdf (513K) GUID:?514B8128-1B6A-4BCF-ADFD-8945AF1CB772 Abstract The lysosome has a key role in the presentation of lipid antigens by CD1 molecules. (
  • In addition, adipocytes could modulate the function and activation of iNKT cells via high expression of CD1d molecules in adipose tissue. (
  • The binding strength between two molecules (e.g., antibody and antigen) taking into account the valency of the interaction. (
  • Crystal Structures of Bovine CD1d Reveal Altered αGalCer Presentation and a Restricted A' Pocket Unable to Bind Long-Chain Glycolipids. (
  • Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells. (
  • Using model carbohydrate systems (isogloboside 3 and B blood group antigen), we examined the anti-carbohydrate response on glycolipids using both antibody neutralisation and knockout mouse-based experiments. (
  • These studies showed that CD4(+) T cells were required to generate antibodies to the carbohydrates expressed on glycolipids, and unexpectedly, these antibody responses were CD1d and NKT cell independent. (
  • CD1d presentation of glycolipids. (
  • After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance specific anti-tumor activity. (
  • These data provide new insight into glycolipid antigen recognition by the immune system and indicate the existence of a previously unrecognised population of glycolipid antigen-specific, CD1-independent, CD4(+) T cells. (
  • CD1d plays a role in non-peptide glycolipid antigen presentation to CD1d-restricted T cells. (
  • Finally, we propose that self, rather than parasite-derived, CD1d-restricted ligands are implicated in iNKT cell stimulation. (
  • This review will cover essential background to iNKT cell and CD1d biology with emphasis on the candidate iNKT cell ligands proposed to date. (
  • Cutting edge: nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells. (
  • His primary areas of study are Immunology, Immune system, Antigen, Molecular biology and Immunoglobulin G. His research integrates issues of Intestinal mucosa and Inflammatory bowel disease in his study of Immunology. (
  • His primary scientific interests are in Immunology, Cell biology, Immune system, Molecular biology and Antigen. (
  • Unconventional T cells follow specific selection rules and are poised to recognize self or evolutionarily conserved microbial antigens. (
  • They recognize lipids presented by of CD1d, in particular the marine-sponge-derived alpha-galactosylceramide (αGC), and express a canonical invariant TCR α chain (Vα24Jα18 in humans and Vα14Jα18 in mice) and TCR β chains that use limited Vβ segments (Vβ11 in humans and Vβ8.2 in mice) ( 4 ). (
  • During her PhD, she discovered and characterized a novel subset of NKT cells with distinct antigen reactivity for a microbial antigen, and revealed that NKT cells express a highly diverse TCR repertoire and utilize broader mechanisms to recognize their cognate antigens, than previously assumed. (
  • Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. (
  • Invariant NKT cells (iNKT cells) recognize CD1d/glycolipid complexes. (
  • The immune system utilizes distinct classes of lipids as antigens which binds glycoproteins called CD1d and activates specific immune cell called NKT cell. (
  • The immunomodulatory glycolipid α-galactosylceramide (α-GalCer) binds to CD1d and exhibits potent activity as a ligand for invariant CD1d-restricted natural killer-like T cells (iNKT cells). (
  • they are self-renewing, and frequently secrete high levels of antibody, which binds to a range of antigens ("polyspecificity") with a relatively low affinity. (
  • It plays a unique role in the presentation of lipid ANTIGENS to NATURAL KILLER T-CELLS. (
  • The aim of this experiment is to validate, this specific lipid antigen synthesized during ER stress. (
  • In vitro assays are established wherein ER stress is induced in J774.2 cells and specific enzymes involved in synthesizing this lipid antigen are inhibited with Fumonisin B 1 or Myriocin in the presence of ER stress inducer Thapsigargin and then co-cultured with NKT cell hybridoma (2C12). (
  • The effects of L-serine on this lipid antigen synthesis during ER stress is also addressed. (
  • Acquired data suggests that the lipid antigen is synthesized during ER stress in J774.2 and can activate CD1d-restricted NKT cells. (
  • Data_Sheet_1.pdf (513K) GUID:?514B8128-1B6A-4BCF-ADFD-8945AF1CB772 Supplementary Physique 3: Statistical analysis of CD1b-restricted lipid antigen presentation by Mo-DCs. (
  • Data_Sheet_1.pdf (513K) GUID:?514B8128-1B6A-4BCF-ADFD-8945AF1CB772 Supplementary Body 6: Statistical evaluation of Compact disc1d-restricted lipid antigen display by Mo-DCs. (
  • While defects in lipid antigen presentation hN-CoR and in invariant Natural Killer T (iNKT) cell response were detected in several mouse models of lysosomal storage diseases (LSD), the impact of lysosomal engorgement in human lipid antigen presentation is poorly characterized. (
  • Structural analogues of α-GalCer have been synthesised to determine which components are required for CD1d presentation and iNKT cell activation, however, to date the importance of the phytosphingosine 4-hydroxyl for iNKT cell activation has been disputed. (
  • Threitolceramide-pulsed DCs are more resistant to iNKT cell-dependent lysis than alpha-galactosylceramide-pulsed DCs due to the weaker affinity of the human iNKT TCR for CD1d/ threitolceramide than CD1d/alpha-galactosylceramide complexes. (
  • d) Mature antigen-capturing DCs induce long-lived, adaptive T-cell immunity. (
  • The inciting antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. (
  • These cells can be stimulated by α-galactosylceramide (α-GalCer) bound to CD1d to induce the production of IFNγ, activation of NK cells, and in situ maturation of dendritic cells (DCs). (
  • In summary, current models hold that tumor antigens are present and induce immune reactivity during incipient tumor growth and that tumors subsequently develop properties to evade these immune responses. (
  • At least four human CD1 proteins, CD1a, CD1b, CD1c, and CD1d, bind lipid Ags within a hydrophobic groove to form antigenic CD1-lipid complexes. (
  • Data_Sheet_1.pdf (513K) GUID:?514B8128-1B6A-4BCF-ADFD-8945AF1CB772 Supplementary Table 1: CD1b, CD1d, and CD80 expression* on Mo-DCs from LSD patients. (
  • The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. (
  • The strength of binding (affinity constant) between a receptor (e.g., one antigen-binding site on an antibody) and a ligand (e.g., epitope on an antigen). (
  • The purified ligand is then released by disrupting the antibody-antigen interaction, for example by changing the pH. (
  • The evidence for an autoimmune etiology includes pathological findings of infiltrating T cells, the presence of antigen-antibody complexes in affected cartilage, cellular and humoral responses against collagen type II and other collagen antigens, and the observation that immunosuppressive regimens most often suppress the disease. (
  • The use of immobilized antibody (or antigen) to select specific antigen (or antibody) from a mixture. (
  • An artificially produced hybrid antibody in which each of the two antigen-binding arms is specific for a different antigenic epitope. (
  • CD1d, known as CD1.1 and Ly-38, is a 48 kD type I membrane glycoprotein with structural similarities to MHC class I and is non-covalently associated with β2-microglobulin. (
  • 13 , 14 α-Galactosylceramide (α-GalCer), a glycolipid extracted from the marine sponge Agelas mauritiana , can stimulate NKT cells to produce enormous amounts of both Th1 and Th2 cytokines in a CD1d-dependent way. (
  • Stimulation of iNKT cells by the CD1d-αGC complex leads to a rapid production of Th1 and Th2 cytokines (e.g. (
  • injection of free αGalCer and injection of CD1d-αGalCer complexes. (
  • CD1d-αGalCer complexes are generally produced by bone marrow-derived dendritic cells pulsed with αGalCer (DCG) in vitro . (
  • NKT cells will reciprocally activate its antigen presenting cell upon lipid/glycolipid presentation. (
  • We also report that schistosome egg-sensitized dendritic cells (DCs) activate, in a CD1d-dependent manner, iNKT cells to secrete IFN-gamma and IL-4 in vitro. (
  • These DCs then changed or matured to mount an immune response by presenting tumor antigen peptide in such a way as to stimulate the production CD4+ and CD8+ T-cells against that particular tumor (cross-presentation 1) (Fig. 1c). (
  • c) Next, DCs engulf tumor debris and cross-present on CD1d to NKT cells, which matures the DCs. (
  • The aAVCs used in this study were allogeneic HEK293 ectopically expressing the AML tumor antigen Wilms' tumor antigen 1 (WT1), which was expressed intracellularly, and CD1d, which could form an αGalCer-CD1d complex on the cell surface. (
  • Such antibodies, which can be produced either by chemical cross-linkage or by recombinant DNA techniques, can be used to link together two different antigens or cells (e.g., a cytotoxic T-cell and a tumor cell). (
  • iNKT cells are positively selected in the thymus in the same manner as major histocompatibility complex restricted T cells, except iNKT cells require CD1d to be presented by thymocytes rather than epithelial cells. (
  • Immunity mediated by lymphocytes and characterized by antigen specificity and memory. (
  • 2004. "Utilizing the Adjuvant Properties of CD1d-Dependent NK T Cells in T Cell-Mediated Immunotherapy. (
  • developed a novel therapeutic vaccine platform consisting of antigen-expressing artificial adjuvant vector cells (aAVC). (
  • Since the vector cells used were HLA-A*02:01 and not HLA-A24, these could not directly present WT1 to these tetramer + T cells, suggesting DC-mediated antigen cross-presentation had taken place in these patients. (
  • NKT cells are now better characterized as CD1d-dependent T cells with potent cytokine production capacity ( 1 - 3 ). (
  • His Immunoglobulin G research incorporates themes from Receptor, Histocompatibility Antigens Class I and Immunotherapy. (
  • Any substance that nonspecifically enhances the immune response to antigen. (
  • The phenomenon whereby, following successful rearrangement of one allele of an antigen receptor gene, rearrangement of the other parental allele is suppressed. (
  • This process enhances T cell immunity to antigens presented by the DC. (
  • 15 Glycosphingolipids (GSLs) isolated from lipopolysaccharide-free Gram-negative bacteria Sphingomonas paucimobilis have the ability to stimulate NKT cells in a CD1d-dependent manner. (
  • Mouse CD1d-restricted NKT cells, including invariant (i)NKT cells, are innate cells activated by glycolipid Ags and play important roles in the initiation and regulation of immune responses. (
  • The effects of the inhibitors on CD1d surface expression in J774.2 are also tested. (
  • Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis of human African trypanosomiasis. (
  • He combines subjects such as Gut flora, Colitis, Homeostasis and Natural killer T cell, CD1D with his study of Inflammation. (
  • Dentro de las distintas células linfoides innatas haremos especial hincapié en una subpoblación con diversas particularidades, las células T natural killer , un subtipo de linfocitos T que expresan receptores de células T y NK. (
  • Natural Killer T (NKT) cellen spelen een belangrijke rol in de bescherming van het individu tegen infecties, tumorontwikkeling en de preventie van auto-immuunziekten. (
  • Invariant natural killer T (iNKT) cells are CD1d-restricted innate-like αβ-T cells expressing an invariant T cell receptor (TCR). (
  • Its lead product candidate, LAVA-051, is advancing toward a Phase 1/2a clinical trial for the treatment of CD1d-expressing hematologic cancers, including chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemia. (
  • 3 Antigen Presentation Research Group. (
  • CD31 + EC may play an antigen-presenting role to iNKT cells after αGalCer treatment and may be a cause of lethal injury. (