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 GUCY2D knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
Fast delivery of KDM4D 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. ...
DNA molecule models and "simple" organic molecule models is what you will find in this shop. They come in all shapes and sizes. From full color models in sandstone to jewelry in all kinds of metals. Please look around and see if there is anything you like :-).
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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 ...
... 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 ...
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 on the surface of cortical epithelial ...
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 ...
... 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 ...
Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens ... Like other 'unconventional' T cell subsets bearing invariant T cell receptors (TCRs), such as CD1d-restricted Natural Killer T ... Dendritic cells are very important in the process of antigen presentation, and serve as a link between the innate and adaptive ... causing the death of the pathogen rid the body of neutralised antigen-antibody complexes. There are three different complement ...
The antigens recognized by non-Vδ2 T cells expanded in the above infectious contexts have not been characterized, but the fact ... Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted Natural Killer T cells, gamma delta ... It is still not clear whether these non-peptidic antigens bind directly to the Vγ9/Vδ2 TCR or if a presenting element exists. ... However, none of the known antigen-presenting molecules like MHC class I and II or CD1 are required for γδ T cell activation ...
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 ...
NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ... Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen ... T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help.[57] Antigen ... Antigen discrimination[edit]. A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. ...
... histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is ... Sköld M, Behar SM (2003). "Role of CD1d-Restricted NKT Cells in Microbial Immunity". Infect. Immun. 71 (10): 5447-55. doi: ... McIntire RH, Hunt JS (2005). "Antigen presenting cells and HLA-G--a review". Placenta. 26 Suppl A: S104-9. doi:10.1016/j. ... "Entrez Gene: HLA-G HLA-G histocompatibility antigen, class I, G". Castelli, Erick C.; Mendes-Junior, Celso T.; Veiga-Castelli, ...
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/ ...
Kompleks antigen-PHK prepoznajo tudi koreceptorji CD4, ki novačijo molekule iz T-celice (npr. Lck tirozinsko kinazo), ki so ... Kot druge "nekonvencionalne" podskupine T-celic z nespremenljivimi receptorji TCR, kot so na CD1d omejene naravne T-celice ... "Vitamin D controls T cell antigen receptor signaling and activation of human T cells". Nature Immunology. Vol. 11 no. 4. Apr ... Le-ta nato potuje po telesu in išče celice, kjer PHK I nosi ta antigen. Ob stiku s takšno celico sprosti citotoksične snovi, ...
... 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 ...
Exogenous antigensEdit. Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. ... Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted natural killer T cells, γδ T cells ... Antigen presentationEdit. Main article: Antigen presentation. Acquired immunity relies on the capacity of immune cells to ... Endogenous antigensEdit. Endogenous antigens are produced by intracellular bacteria and viruses replicating within a host cell ...
"Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum". J. Biol. Chem. 285 (49): 38283-92 ... "A human Ro/SS-A autoantigen is the homologue of calreticulin and is highly homologous with onchocercal RAL-1 antigen and an ...
Memorijske T ćelije su podskup antigen - specifičnih T ćelijs koje traju dugoročno nakon savladavanja infekcije.[1] One se brzo ... ćelije prepoznaju glikolipidne antigene predstavljene molekulama pod nazivom CD1d. Kada se aktiviraju, ove ćelije mogu ... Ove ćelije prepoznaju svoje ciljeve putem vezanja za antigen koji je asociran sa molekulama MHC klase I, koje se ispoljavaju na ... MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. 2009 ...
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 ( ... ATP Binding Cassette Transporter ABCA7 Regulates NKT Cell Development and Function by Controlling CD1d Expression and Lipid ... "ATP Binding Cassette Transporter ABCA7 Regulates NKT Cell Development and Function by Controlling CD1d Expression and Lipid ...
自然杀伤T细胞(NKT细胞),请不要把它和固有免疫中的自然杀伤细胞(NK细胞)混淆。 与一般T细胞识别MHC分子上的肽链抗原不同,NKT识别的是CD1d分子上结合的糖蛋白抗原。被激活后,它们可以执行类似辅助T细胞和细胞毒性T细胞的功能,即释放细胞因子和细 ... MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proceedings of the National ...
自然杀伤T细胞(NKT细胞),请不要把它和固有免疫中的自然杀伤细胞(NK细胞)混淆。 与一般T细胞识别MHC分子上的肽链抗原不同,NKT识别的是CD1d分子上结合的糖蛋白抗原。被激活后,它们可以执行类似辅助T细胞和细胞毒性T细胞的功能,即释放细胞因子和细 ... MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proceedings of the National ...
Memorijske T ćelije su podskup antigen - specifičnih T ćelijs koje traju dugoročno nakon savladavanja infekcije.[1] One se brzo ... ćelije prepoznaju glikolipidne antigene predstavljene molekulama pod nazivom CD1d. Kada se aktiviraju, ove ćelije mogu ... Ove ćelije prepoznaju svoje ciljeve putem vezanja za antigen koji je asociran sa molekulama MHC klase I, koje se ispoljavaju na ... MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. 2009 ...
NKT cells recognize glycolipid antigen presented by CD1d. Once activated, these cells can perform functions ascribed to both Th ... Antigen-naïve 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.[51] Antigen ... Antigen discriminationEdit. A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. ...
Cell-free antigen presentation assay.. Antigen presentation experiments using wild-type or point-mutated CD1d molecules and V ... Mice express only CD1d. Crystal structures of human CD1a, b, and d, as well as mouse CD1d, without loading specific antigens, ... when it was presented by heterologous human CD1d. Surprisingly, and unlike GSL antigens, borrelial α-GalDAG antigens can bind ... We show that CD1d binding of the borrelial α-GalDAG antigens is relatively promiscuous, in that it included some nonantigenic ...
Glycolipid Antigen Processing for Presentation by CD1d Molecules Message Subject. (Your Name) has forwarded a page to you from ... Glycolipid Antigen Processing for Presentation by CD1d Molecules. By Theodore I. Prigozy, Olga Naidenko, Pankaj Qasba, Dirk ... Glycolipid Antigen Processing for Presentation by CD1d Molecules. By Theodore I. Prigozy, Olga Naidenko, Pankaj Qasba, Dirk ... The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to ...
CD1d is a key antigen-presenting molecule involved in the selection and activation of a highly conserved T cell subset known as ... Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells.. Spada FM1, Borriello F, Sugita ... In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of ... and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. Overall, these ...
Identification of CD1d-associated Lipid Antigens by Shotgun Lipidomics. Lipids are playing important roles in regulating immune ... They can be recognized by T cells as antigens when presented by atypical MHC class I proteins of the CD1 family1. The CD1-lipid ...
... iNKT cells have an antigen-experienced phenotype and can respond very rapidly to CD1d-presented antigens without the need for ... 1998) CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. J Exp Med 188:1529-1534.. ... 2001) Glycolipid antigen processing for presentation by CD1d molecules. Science 291:664-667.. ... B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in ...
... Nat Immunol ... antigen presentation and T cell development, demonstrating the critical functions of the CD1d cytoplasmic tail motif in vivo. ... we now describe knock-in mice with the CD1d cytoplasmic tail deleted. Despite adequate surface CD1d expression and the presence ... Little is known about the intracellular pathways of CD1 trafficking and antigen presentation. However, in vitro studies with ...
1999) CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science. 283:225-229, pmid: ... 1998) CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. J. Exp. Med. 188:1529-1534 ... Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers. Jennifer L. Matsuda, Olga V. ... Dimeric CD1d-α-GalCer Complexes.. Soluble recombinant mCD1d1 and human (h)CD1d proteins expressed in Drosophila SC2 cells have ...
BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand. ... BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand ... BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand ... BAFF- and APRIL-Dependent Maintenance of Antibody Titers after Immunization with T-Dependent Antigen and CD1d-Binding Ligand ...
Intervista: Antigen Presentazione glicolipide da CD1d e il potenziale terapeutico di attivazione delle cellule NKT. ...
The types of lipids loaded initially onto CD1d could affect the ability of the CD1d antigen to be edited by saposins or other ... also regulates CD1d presentation of glycolipid antigens in the liver and intestine. We show MTP RNA and protein in antigen- ... Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells Stephanie K. Dougan ... Tail-deleted forms of CD1d that fail to traffic to endosomes activate Vα14− NK1.1− NKT cells but cannot present antigen to ...
The actin cytoskeleton modulates the activation of invariant NKT cells by segregating CD1d nanoclusters on antigen presenting ... The actin cytoskeleton modulates the activation of invariant NKT cells by segregating CD1d nanoclusters on antigen presenting ...
Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T- ... The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. ...
N2 - Invariant natural killer T (iNKT) cells recognize glycolipid antigens presented by CD1d, an antigen presenting protein ... AB - Invariant natural killer T (iNKT) cells recognize glycolipid antigens presented by CD1d, an antigen presenting protein ... Invariant natural killer T (iNKT) cells recognize glycolipid antigens presented by CD1d, an antigen presenting protein ... abstract = "Invariant natural killer T (iNKT) cells recognize glycolipid antigens presented by CD1d, an antigen presenting ...
CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. Journal of Experimental Medicine ... CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells. / Spada, Franca M.; Koezuka, ... Spada, F. M., Koezuka, Y., & Porcelli, S. A. (1998). CD1d-restricted recognition of synthetic glycolipid antigens by human ... Spada, Franca M. ; Koezuka, Yasuhiko ; Porcelli, Steven A. / CD1d-restricted recognition of synthetic glycolipid antigens by ...
Structural studies identify considerable differences in the recognition of CD1d-lipid complexes by the TCRs of type II and type ... Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor *Onisha Patel ... Figure 1: Differences in the recognition of CD1d by type II NKT cell TCRs and type I iNKT cell TCRs.. ... Type II natural killer T cells use features of both innate-like and conventional T cells to recognize sulfatide self antigens * ...
CD1d is a type I transmembrane protein and member of the MHC family, with a molecular weight ranging from 43-49 kD, depending ... CD1d is expressed by antigen presenting cells such as dendritic cells, monocytes, macrophages and B cells; also expressed by ... Antigen-presenting glycoprotein CD1d1, CD1.1, Ly-38 Isotype Mouse IgG1, κ Ave. Rating Submit a Review Product Citations ... Antigen References 1. Arrenberg P, et al. 2010. P. Natl. Acad. Sci. USA 107:10984.. 2. Mattarollo SR, et al. 2010. J. Immunol. ...
CD1d is a MHC-like, type I transmembrane protein, member of the CD1 family and the immunoglobulin superfamily. ... Cortical thymocytes express CD1d but the expression is lost in mature T cells. CD1d presents lipid antigens to iNKT cells ... On the cell surface, CD1d forms a heterodimer with β2-microglobulin. CD1d is expressed by antigen-presenting cells such as B ... CD Molecules, MHC Antigens, TCRs Antigen References 1. Koch M, et al. 2005. Nat. Immunol. 6:819.. 2. Liu X, et al. 2010. P. ...
... Academic Article ... suggesting the absence of a CD1d-specific, antigen-nonspecific NK receptor. Mouse CD1d1-alphaGalCer tetramers also stained ... Here, we report the generation and use of mouse CD1d1-glycolipid tetramers to visualize CD1d-restricted T cells. In contrast ... Fluorescent tetramers of mouse CD1d1 complexed with alpha-galactosylceramide (alphaGalCer), the antigen recognized by mouse ...
Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface. Proceedings of the National Academy ... Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface ...
Glycolipid Antigen Processing for Presentation by CD1d Molecules. By Theodore I. Prigozy, Olga Naidenko, Pankaj Qasba, Dirk ...
Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells. Eur. J. Immunol. 30:3468. ... Detection of the expression of CD1d in Jurkat T cells. A, Detection of CD1D transcripts by RT-PCR. B, Detection of CD1d protein ... Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-γ production by NK-T cells. J. Immunol. 165:4076. ... Activation-induced expression of CD1d antigen on mature T cells. J. Leukocyte Biol. 69:207. ...
NKT cells are reactive to the nonclassical class I antigen-presenting molecule CD1d, and they recognize glycolipid antigens ... Going both ways: immune regulation via CD1d-dependent NKT cells J Clin Invest. 2004 Nov;114(10):1379-88. doi: 10.1172/JCI23594 ...
... as a novel human CD1d receptor that inhibits CD1d-mediated immune responses. We found that native CD1d tetramer generated by ... The interaction between ILT4 and CD1d involves the two N-terminal domains of ILT4 and the Ag-binding groove of CD1d (alpha1/ ... The interaction between ILT4 and CD1d may provide new insights into the regulation of NKT-mediated immunity. ... NKT cells recognize lipid Ags presented by CD1d molecules and play an important role in the regulation of innate and adaptive ...
Shop a large selection of products and learn more about CD1d Rat anti-Mouse, Clone: 1B1, eBioscience 100 µg; Unconjugated 100 ... AI747460, CD1.1, Cd1a, Cd1d, Ly-38, T-cell surface glycoprotein CD1d1, antigen-presenting glycoprotein CD1d1. ... While similar to MHC Class I, CD1d associates with beta2m, functionally CD1d is similar to MHC Class II. 1B1 detects CD1d at ... CD1d is the sole group 2 member of the CD1 family of major histocompatibility (MHC) like glycoproteins. The CD1d gene encodes a ...
Antigen-presenting glycoprotein CD1d1. A. 285. Mus musculus. Mutation(s): 0 Gene Names: Cd1.1, CD1d, Cd1d1. ... Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.. Aspeslagh, S., Li, Y., ... The strength of the Th1 response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism ... This induced fit is in contrast to another Th1-biasing glycolipid, α-C-GalCer, whose CD1d binding follows a conventional key- ...
Structure of the mouse CD1d-PyrC-alpha-GalCer-iNKT TCR complex ... Antigen-presenting glycoprotein CD1d1. A. 285. Mus musculus. ... NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. Although it was ... NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. Although it was ... Structure of the mouse CD1d-PyrC-alpha-GalCer-iNKT TCR complex. *DOI: 10.2210/pdb4IRS/pdb ...
The ELISA (enzyme-linked immunosorbent assay) is a well-established antibody-based tool for detecting and quantifying antigens ... Human Antigen-presenting glycoprotein CD1d, CD1D ELISA Kit *. Detection Target: CD1d molecule ...
... has been identified as a potent CD1d-presented self-antigen for mouse invariant natural killer T (iNKT) cells. The role of iGb3 ... Antigen Presentation. Antigens, CD1d / chemistry, immunology*, metabolism. Globosides / immunology*, metabolism. Humans. ... 0/Amino Acids; 0/Antigens, CD1d; 0/Globosides; 0/Receptors, Antigen, T-Cell; 0/Trihexosylceramides; 0/ ... Isoglobotrihexosylceramide (iGb3) has been identified as a potent CD1d-presented self-antigen for mouse invariant natural ...
CD1d) and the T cell receptors. However, these structures alone do not reveal the relative importance of these interactions. ... reactive Type II NKT cells have shown how the polar moieties on the glycolipids interact with both the antigen presenting ... Structural studies of ternary complexes of CD1d/glycosyl ceramides/iNKT cells and CD1d/sulfatide/sulfatide ... Keywords: β-GalCer; antigens; NKT cells; CD1d β-GalCer; antigens; NKT cells; CD1d ...
The MHC class-I like molecule CD1d presents glycolipid antigens and thereby. By Abigail Sims , Published December 14, 2017 ... The MHC class-I like molecule CD1d presents glycolipid antigens and thereby activates invariant natural killer-T (NKT) cells. ... disc38 differentially regulate Compact disc1n proteins localization in THP-1 cells Since Compact disc1n is certainly an antigen ...
  • CD1d was expressed as a mature glycoprotein by these cells, and unlike the other members of the human CD1 family its expression was constitutive and was not strongly up-regulated by GM-CSF and IL-4 or a range of other cytokines. (
  • Description: The 1B1 monoclonal antibody reacts with mouse CD1d, a 48 kDa glycoprotein with structural homology to MHC class I molecules. (
  • Clone 1B1 reacts with CD1d, also known as CD1.1 and Ly-38, a 48 kDa type I membrane glycoprotein with structural homology to MHC class I molecules. (
  • CD1d is a key antigen-presenting molecule involved in the selection and activation of a highly conserved T cell subset known as NK T cells. (
  • NK T lymphocytes may be classified into those that are positively selected by CD1d, a nonclassical class I molecule (for review see reference 1), and those that are CD1d independent. (
  • CD1d presents lipid antigens to i NKT cells analogous to MHC molecule presentation of peptides to T cells. (
  • After investigating 3.7 kb 5′ upstream of the coding region, we found that human gene encoding CD1d molecule (CD1D) has TATA boxless dual promoters with multiple transcription initiation sites. (
  • The gene encoding CD1d molecule (CD1D) 3 gene belongs to the group II CD1 gene family in human. (
  • Among the CD1 molecules, CD1d is highly conserved across species and is the only group CD1 molecule functionally present in mice and rats ( 8 , 9 , 10 , 11 ). (
  • In stark contrast to both conventional T lymphocytes and other types of Tregs, NKT cells are reactive to the nonclassical class I antigen-presenting molecule CD1d, and they recognize glycolipid antigens rather than peptides. (
  • The MHC class-I like molecule CD1d presents glycolipid antigens and thereby activates invariant natural killer-T (NKT) cells. (
  • RA and Compact disc38 differentially regulate Compact disc1n proteins localization in THP-1 cells Since Compact disc1n is certainly an antigen-presenting molecule, we additional examined its phrase and mobile distribution by movement cytometry and confocal microscopy. (
  • CD1d, a non-polymorphic MHC class I-like molecule, presents lipid antigens to Natural killer T (NKT) cells, which have potent anti-tumor effector functions. (
  • Pretreatment with Trichostatin A (TSA) resulted in a dose-dependent increase in CD1d-mediated NKT cell activation by lymphoma cells without altering CD1d or co-stimulatory molecule cell surface expression. (
  • The CD1d molecule shows a homology with MHC class I (MHC-I) polypeptides and is expressed in several cell types including dendritic cells, macrophages, and B cells ( 18 ). (
  • Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. (
  • All invariant Valpha24(+) clones recognized the MHC class I-like CD16 molecule and discriminated between CD1d and other closely related human CD1 proteins, indicating that recognition was TCR-mediated. (
  • These cells recognize different glycolipid antigens through the CD1d molecule. (
  • Because they recognize a glycolipid antigen produced by a molecule called CD1d. (
  • Invariant natural killer T cells (iNKT cells) respond to CD1d-presented glycolipids from Borrelia burgdorferi , the causative agent of Lyme disease. (
  • Although mouse and human iNKT cells respond to different antigens based on subtle differences in their fatty acids, the mechanism by which fatty acid structure determines antigenic potency is not well understood. (
  • CD1 molecules recycle through intracellular vesicular compartments, where they sample different lipid-containing antigens for cell-surface presentation to reactive T cells ( 2 ⇓ - 4 ). (
  • A specialized subset of glycolipid and CD1d-restricted T lymphocytes are known as type I or semi-invariant (i) natural killer T (NKT) cells. (
  • These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids. (
  • Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells. (
  • In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of myeloid origin, including circulating monocytes, monocyte-derived dendritic cells and macrophages. (
  • Despite their remarkably low surface expression of CD1d, all myeloid lineage cells tested were extremely potent APC for responses of NK T cell clones to the synthetic glycolipid antigen, alpha-galactosyl ceramide. (
  • Prominent localization of CD1d to the endocytic system of monocyte lineage cells was observed, and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. (
  • Overall, these results support the view that monocyte lineage cells are important stimulators of CD1d-restricted immune responses, while also underscoring the unique regulation of CD1d expression by these cells. (
  • They can be recognized by T cells as antigens when presented by atypical MHC class I proteins of the CD1 family1. (
  • To elicit antibody production, B cells must be activated in a process that is initiated through specific antigen recognition by the B cell receptor (BCR) ( 1 ). (
  • Specific antigen engagement initiates two BCR-mediated processes: the transmission of intracellular signals regulating entry into cell cycle ( 2 , 3 ) and antigen internalization before its processing and presentation in association with MHC to specific T cells ( 4 ). (
  • In a manner similar to MHC class II molecules, CD1 proteins mediate the presentation of antigenic lipids on the surface of antigen-presenting cells (APCs) after they are loaded or processed in intracellular compartments ( 10 ). (
  • As CD1d is expressed by B cells, it is conceivable that BCR-mediated internalization could also play a role in CD1d-dependent presentation of antigenic lipids to T cells. (
  • T cells recognize a diverse range of potential antigens through their highly polymorphic T cell receptor (TCR). (
  • iNKT cells recognize and become activated in response to self or foreign antigenic lipids presented by nonpolymorphic CD1d molecules expressed on the surface of APCs ( 8 , 11 ). (
  • By introducing a deletion of the tyrosine motif into the germ line, and through homologous recombination in embryonic stem cells, we now describe knock-in mice with the CD1d cytoplasmic tail deleted. (
  • A major group of natural killer (NK) T cells express an invariant Vα14 + T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. (
  • Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14 + NK T cells. (
  • Many members of this first population, the CD1d-dependent NK T cells, express a semiinvariant TCR composed of a specific Vα14 rearrangement paired preferentially with a diverse set of Vβ8.2, Vβ7, or Vβ2 rearrangements. (
  • CD1d-dependent NK T cells are believed to be involved in the regulation of immune responses as a result of their potent ability to secrete cytokines. (
  • CD1d-dependent NK T cells also might be involved in some circumstances in the prevention of tumor metastases ( 9 ) and the response to some infectious agents ( 10 )( 11 )( 12 )( 13 ). (
  • Currently, the natural ligand(s) for CD1d-restricted NK T cells is unknown, although phosphoinositol-containing compounds have been suggested to be natural ligands for some of these cells ( 13 )( 14 )( 15 ). (
  • α-GalCer is a specific agent for activating Vα14 + CD1d-dependent NK T cells ( 16 )( 18 ). (
  • Although analysis for the coexpression of NK1.1 and an α/β TCR is widely used to identify CD1d-dependent NK T cells, there are several reasons why this method is not entirely satisfactory. (
  • Second, NK1.1 + T cells may downregulate the NK1.1 marker upon activation ( 24 ), making it difficult to follow these cells once they have encountered antigen. (
  • Lastly, the NK1.1 marker also is found on CD1d-independent T cells ( 25 )( 26 )( 27 ). (
  • Tetramers have been used widely to obtain a detailed analysis of the distribution and frequency of conventional CD4 + and CD8 + antigen-specific T cells during a variety of immune responses. (
  • CD1d-restricted invariant NKT (iNKT) cells boost humoral immunity to T-dependent Ags that are coadministered with the CD1d-binding glycolipid Ag α-galactosylceramide (α-GC). (
  • Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells. (
  • The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. (
  • Invariant natural killer T (iNKT) cells recognize glycolipid antigens presented by CD1d, an antigen presenting protein structurally similar to MHC class I. Stimulation of iNKT cells by glycolipid antigens can induce strong immune responses in vivo, with rapid production of a wide variety of cytokines including those classically associated with either T helper type 1 (Th1) or type 2 (Th2) responses. (
  • Here we show that neutralization of endosomal pH enhanced localization of CD1d complexes containing Th2-biasing glycolipids to plasma membrane lipid rafts of antigen presenting cells (APC). (
  • Here we show that human NK T cell clones are strongly and specifically activated by the same synthetic glycolipid antigens as have been shown recently to stimulate murine NK T cells. (
  • Responses of human NK T cells to these synthetic glycolipids, consisting of certain α-anomeric sugars conjugated to an acylated phytosphingosine base, required presentation by antigen-presenting cells expressing the major histocompatibility complex class I-like CD1d protein. (
  • Presentation of synthetic glycolipid antigens to human NK T cells required internalization of the glycolipids by the antigen-presenting cell and normal endosomal targeting of CD1d. (
  • Spada, FM, Koezuka, Y & Porcelli, SA 1998, ' CD1d-restricted recognition of synthetic glycolipid antigens by human natural killer T cells ', Journal of Experimental Medicine , vol. 188, no. 8, pp. 1529-1534. (
  • Structural studies identify considerable differences in the recognition of CD1d-lipid complexes by the TCRs of type II and type I (invariant) natural killer T cells. (
  • Here, we report the generation and use of mouse CD1d1-glycolipid tetramers to visualize CD1d-restricted T cells. (
  • In contrast, natural killer (NK) cells failed to bind the tetramers either empty or loaded with alphaGalCer, suggesting the absence of a CD1d-specific, antigen-nonspecific NK receptor. (
  • CD1d present glycolipids to i NKT cells that recognize them by their Vα14 i TCR. (
  • CD1d is expressed by antigen-presenting cells such as B cells, monocytes/macrophages, dendritic cells, and some non-lymphoid cells. (
  • Cortical thymocytes express CD1d but the expression is lost in mature T cells. (
  • NKT cells recognize lipid Ags presented by CD1d molecules and play an important role in the regulation of innate and adaptive immune responses. (
  • We found that native CD1d tetramer generated by mammalian cells was able to specifically bind human monocytes in the peripheral blood, and this binding was at least partly mediated by monocyte-expressed ILT4. (
  • CD1d presents lipid Ags to a specific population of NK T cells, which are involved in the host immune defense, suppression of autoimmunity, and the rejection of tumor cells. (
  • The illustration of the dual CD1D gene promoters will help to reveal the regulatory factors that control CD1d expression and its tissue distribution for a better understanding of the cross-regulation between CD1d and NK T cells. (
  • Both human and mouse CD1d can present α-galactosylceramide to NK T cells, which express a restricted range of TCRs bearing a single invariant Vα chain (Vα14Jα281 in mice and Vα24 inv in human) to stimulate specific immune responses ( 12 , 13 ). (
  • Human CD1d expression can be up-regulated on intestinal epithelial cells and keratinocytes by IFN-γ ( 20 , 21 ) or on peripheral blood T cells by mitogen stimulation ( 15 , 22 ). (
  • Overexpression of CD1d has been seen in patients with psoriasis on keratinocytes ( 21 ), in patients with allergic reactions to cow's milk in the duodenal lamina propria ( 23 ), and in patients with primary biliary cirrhosis on the epithelial cells of the small bile ducts ( 24 ). (
  • The levels of CD1d expression can vary significantly between different individuals on T lymphocytes ( 15 ), monocytes, or monocyte-derived dendritic cells ( 25 ). (
  • Beta 2 microglobulin independent expression of CD1d has also been demonstrated on human intestinal epithelial cells. (
  • Structural studies of ternary complexes of CD1d/glycosyl ceramides/ i NKT cells and CD1d/sulfatide/sulfatide reactive Type II NKT cells have shown how the polar moieties on the glycolipids interact with both the antigen presenting protein (CD1d) and the T cell receptors. (
  • These findings highlight the previously unexploited flexibility of CD1d in accommodating galactose-modified glycolipids and broaden the range of glycolipids that can stimulate iNKT cells. (
  • NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. (
  • CD1d protein structure determines species-selective antigenicity of isoglobotrihexosylceramide (iGb3) to invariant NKT cells. (
  • Isoglobotrihexosylceramide (iGb3) has been identified as a potent CD1d-presented self-antigen for mouse invariant natural killer T (iNKT) cells. (
  • Here we show that human and mouse iNKT cells were both able to recognise iGb3 presented by mouse CD1d (mCD1d), but not human CD1d (hCD1d), as iGb3-hCD1d was unable to support cognate interactions with the iNKT-cell TCRs tested in this study. (
  • Many hematologic malignancies express CD1d and the co-stimulatory proteins needed to induce anti-tumor responses by NKT cells, yet most tumors are poorly immunogenic. (
  • Here we sought to test the hypothesis that B cell lymphomas use epigenetic mechanisms to dysregulate CD1d-mediated antigen processing and presentation leading to a functional impairment in the ability of NKT cells to recognize tumors. (
  • Similarly, pretreatment with TSA enhanced MHC class II mediated antigen presentation to CD4+ T cells. (
  • In addition, thymocytes and splenocytes from NPC2-deficient mice were poor presenters of endogenous and exogenous lipids to CD1d-restricted Vα14 hybridoma cells. (
  • Similar to saposin B, NPC2 dimers were able to load isoglobotrihexosylceramide (iGb3), the natural selecting ligand of NKT cells in the thymus, into CD1d. (
  • CD1d is the restriction element for two groups of T cells that recognize lipids. (
  • NKT cells represent an ideal system for the study of lipid antigens because agonist ligands such as α-galactosyl and α-glucuronosyl ceramides have been identified, and the main thymic selecting ceramide, isoglobotrihexosylceramide (iGb3), is known ( 9 , 10 ). (
  • The main endogenous self-glycolipid that, once bound to CD1d, selects canonical Vα14 NKT cells was recently identified as iGb3, a sphingolipid that is produced in small quantities by iGb3 synthases and mainly by the degradation of isoglobotetrahexosylceramide by glycosidase β-hexosaminidase b, as illustrated by the absence of Vα14 NKT cells in hexosaminidase b-deficient mice ( 10 , 15 ). (
  • Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation. (
  • To address these questions, we used a combination of cellular assays and demonstrated that saposins influence CD1d-restricted presentation to human iNKT cells not only of exogenous lipids but also of endogenous ligands, such as the self-glycosphingolipid β-glucopyranosylceramide, up-regulated by antigen-presenting cells following bacterial infection. (
  • Furthermore, we demonstrated that in human myeloid cells CD1d-loading of endogenous lipids after bacterial infection, but not at steady state, requires trafficking of CD1d molecules through an endo-lysosomal compartment. (
  • These results have important implications in understanding how to optimize lipid-loading onto antigen-presenting cells, to better harness iNKT cells central role at the interface between innate and adaptive immunity. (
  • Invariant natural killer T (iNKT) cells recognize endogenous and exogenous lipid antigens presented in the context of CD1d molecules. (
  • The ability of iNKT cells to recognize endogenous antigens represents a distinct immune recognition strategy, which underscores the constitutive memory phenotype of iNKT cells and their activation during inflammatory conditions. (
  • Here, we show that the spatiotemporal distribution of CD1d molecules on the surface of antigen-presenting cells (APCs) modulates activation of iNKT cells. (
  • CD1D is the human gene that encodes the protein CD1d, a member of the CD1 (cluster of differentiation 1) family of glycoproteins expressed on the surface of various human antigen-presenting cells. (
  • They are non-classical MHC proteins, related to the class I MHC proteins, and are involved in the presentation of lipid antigens to T cells. (
  • CD1d-presented lipid antigens activate a special class of T cells, known as natural killer T (NKT) cells, through the interaction with the T-cell receptor present on NKT membranes. (
  • The related β-D-glucopyranosylceramide is accumulated in antigen-presenting cells after infection, where it serves to activate invariant NKTs (iNKTs), a special kind of NKT. (
  • CD1d tetramers are protein constructs composed of four CD1d molecules joined together and usually fluorescently labelled, used to identify NKT cells or other CD1d-reactive cells. (
  • Activation of invariant CD1d-dependent NK T 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. (
  • The adjuvant activity of α-GalCer enhances both priming and boosting of CD8+ T cells to coadministered peptide or protein antigens, including a peptide encoding the clinically relevant, HLA-A2-restricted epitope of the human tumor antigen NY-ESO-1. (
  • Importantly, α-GalCer was used to induce CD8+ T cells to antigens delivered orally, despite the fact that this route of administration is normally associated with blunted responses. (
  • B ) Surface expression of CD86 on CD11c + cells was assessed on splenocytes from wild-type C57BL/6 or CD1d-/- mice or a mixture of splenocytes from both (Mixed), stimulated in vitro with (thick solid lines) or without α-GalCer (gray filled histograms) for 16 hours. (
  • D ) The immunostimulatory capacity of splenic CD11c + cells from α-GalCer- or vehicle-treated C57BL/6 (B6) animals was assessed by loading with OVA 257-264 peptide ex vivo and transferring antigen-loaded cells into naive C57BL/6 and i NKT cell-deficient recipients ( n = 5) (arrows indicate direction of DC transfer). (
  • In the current study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. (
  • Accordingly, adipocyte-specific CD1d-knockout (CD1d ADKO ) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide-induced iNKT cell activation. (
  • Additionally, HFD-fed CD1d ADKO mice revealed reduced interleukin-4 expression in adipose iNKT cells and aggravated adipose tissue inflammation and insulin resistance. (
  • iNKT cells are the type I NKT cells that are characterized by the expression of semi-invariant CD1d-restricted T cell receptors (TCRs) ( 18 ). (
  • Also, iNKT cells recognize lipid antigens loaded on CD1d molecules ( 19 ). (
  • Marine sponge-derived α-galactosylceramide (α-GC) is a potent CD1d-binding lipid antigen that activates iNKT cells ( 20 ). (
  • In iNKT cells, determination of cytokine characters into Th1 type or Th2 type is influenced by antigen-presenting cell (APC) types, environmental cytokine milieu, and lipid antigen species ( 18 , 21 ). (
  • Interestingly, adipocytes highly express CD1d and potentially activate iNKT cells in vitro ( 13 , 17 ). (
  • In the current study, we investigated the in vivo roles of adipocyte CD1d in the regulation of adipose iNKT cells, adipose tissue inflammation, and insulin resistance in obesity. (
  • The present experiments suggest that adipocyte CD1d is a crucial activator of adipose iNKT cells and that adipose iNKT cell activation could alleviate adipose tissue inflammation and insulin resistance in obese subjects. (
  • Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. (
  • CD1d-dependent activation of NKT cells aggravates atherosclerosis. (
  • Natural killer T (NKT) cells can recognize lipid antigens presented by CD1 molecules. (
  • We have explored the role of CD1d-restricted NKT cells in atherosclerosis by using apolipoprotein E-deficient (apoE-/-) mice, a hypercholesterolemic mouse model that develops atherosclerosis. (
  • Administration of alpha-galactosylceramide, a synthetic glycolipid that activates NKT cells via CD1d, induced a 50% increase in lesion size in apoE-/- mice, whereas it did not affect lesion size in apoE-/-CD1d-/- mice. (
  • These results show that activation of CD1d-restricted NKT cells exacerbates atherosclerosis. (
  • Together, these findings indicate that CD1d-dependent activation of NKT cells aggravates atherosclerosis and that lack of CD1d, the restriction element for presentation of lipid antigens to NKT cells, leads to reduced lesions in a mouse model of human atherosclerosis. (
  • CD1 molecules, like MHC I and II, play an equally important role in the immune system by presenting lipid, glycolipid and lipopeptide antigen to T and NKT cells. (
  • MHC class II-restricted CD4 + T cells specific for peptide antigens, which acquire professional follicular B cell helper functions, have been long recognized as key players in this process. (
  • CD1d restricted NKT cells specific for lipid antigens are one such new player and can coopt bona fide follicular helper phenotypes. (
  • Their role in helping antigen-specific B cell response to protein antigens, as well as to the so called "help-less" antigens that cannot be recognized by T follicular helper cells, is being increasingly elucidated, highlighting their potential pathophysiological impact on the immune response, as well as on the design of improved vaccine formulations. (
  • Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells. (
  • Upon activation by anti-CD3 or CD1d, the clones produced both Th1 and Th2 cytokines.These results demonstrate that human invariant Valpha24+ CD4-CD8- T cells, and presumably the homologous murine NK1+ T cell population, are CD1d reactive and functionally distinct from NK cells.The conservation of this cell population and of the CD1d ligand across species indicates an important immunological function. (
  • These results demonstrate that human invariant Valpha24+ CD4-CD8- T cells, and presumably the homologous murine NK1+ T cell population, are CD1d reactive and functionally distinct from NK cells. (
  • Although the target cells that mediate activation of invariant Vα24+ T cells in vivo are not known, normal B cells express CD1d (51) and may be a relevant CD1d-presenting cell. (
  • Therefore, the C1R HLA-A and -B negative B lymphoblastoid cell line (52), which does not express detectable CD1d (our unpublished data), was used to confirm the results in CHO cells and to determine whether the need for nonphysiological costimulation could be reduced or eliminated. (
  • CD1d-transfected C1R cells specifically stimulated each of the invariant Vα24+ DN T cell clones tested based upon IFN-γ and IL-4 production and T cell proliferation (Fig. 5 a and data not shown), confirming the results in CHO cells. (
  • CD1d is found at varying levels on most types of bone marrow and peripheral leukocytes and on epithelial, dendritic, and lymphoid cells in the thymus. (
  • Clone 51.1 recognizes CD1d, a member of the CD1 family of MHC class I like glycoproteins involved in presenting lipid-based antigens to T cells. (
  • CD1d-restricted repertoire of T cells include NKT cells expressing invariant chain T cell receptors (TCRs), T cells with diverse TCRs, and naive like T cells with intermediate expression levels of the transcription factor PLZF. (
  • Expression of CD1d is found on the surface of many cells, including hepatocytes and professional antigen-presenting cells (APCs), including splenic dendritic cells (DCs), macrophages and B cells, intestinal epithelial cells, foreskin keratinocytes, penile urethral epithelial cells, and hepatocytes. (
  • 2011) A naive-like population of human CD1d-restricted T cells expressing intermediate levels of promyelocytic leukemia zinc finger. (
  • They differ from conventional αβ T cells, since most of γδ T cells do not express the CD4 and CD8 co-receptors and, as a consequence, antigen recognition by γδ TCR is not restricted to major histo-compatibility complex (MHC) molecules ( 13 , 14 ). (
  • Moreover as γδ T cell activation does not require antigen processing and presentation by antigen-presenting cells (APC), γδ T cells can be rapidly activated and act during the early phase of the immune response. (
  • NKT cells are CD1d-restricted T cells that recognize lipid antigens. (
  • Bai L, Picard D, Anderson B, Chaudhary V, Luoma A, Jabri B, Adams EJ, Savage PB, Bendelac A (2012) The majority of CD1d-sulfatide-specific T cells in human blood use a semiinvariant Vdelta1 TCR. (
  • Sriram V, Du W, Gervay-Hague J, Brutkiewicz RR (2005) Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. (
  • Girardi E, Zajonc DM (2012) Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells. (
  • Pei B, Speak AO, Shepherd D, Butters T, Cerundolo V, Platt FM, Kronenberg M (2011) Diverse endogenous antigens for mouse NKT cells: self-antigens that are not glycosphingolipids. (
  • Human and mouse i NKT cells react to the same glycolipid antigens, including α-galactosylceramide (α-GalCer), which is presented by CD1d. (
  • However, humans have fewer CD1d-restricted i NKT cells than mice. (
  • Additionally, α-GalCer targets only i NKT cells, as there is little bystander activation and little transactivation in mice lacking CD1d. (
  • Moreover, activation of iNKT cells is determined by the type and state of the antigen presenting cell, the co-stimulatory molecules, the transactivation mechanisms and the location of the glycolipid-CD1d complexes on the plasma membrane, such as the lipid rafts. (
  • Explores the antigen-recognition properties of murine gamma/delta T cells. (
  • The success of vaccination is directly or indirectly based on the specificity of antigen recognition by T lymphocytes, their efficient activation and expansion, and the generation of vaccine-specific effector and memory cells. (
  • Glycolipids presented by the major histocompatibility complex (MHC) class I homolog CD1d are recognized by natural killer T cells (NKT cells) characterized by either a semi-invariant T cell antigen receptor (TCR) repertoire (type I NKT cells or iNKT cells) or a relatively variable TCR repertoire. (
  • The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8+ T cells to respond to foreign antigens. (
  • The strength with which complexes of self peptide and major histocompatibility complex (MHC) proteins are recognized by the T cell antigen receptor (TCR) dictates the homeostasis of naive CD8+ T cells, but its effect on reactivity to foreign antigens is controversial. (
  • In the past 15 years, the molecular identification of antigens that can mediate the killing of tumor cells by T cells has been vigorously pursued. (
  • Identification, isolation and characterization of multiple antigen-specific populations of T cells by Soen et al. (
  • It has the ability to recognize autologous cells expressing foreign antigens. (
  • There are lots of different types of T-cells, but the ones that do the killing of antigens that are foreign to the system are natural killer T-cells, or NKT cells. (
  • Group 1 CD1-restricted T cells and the pathophysiological implications of self-lipid antigen recognition. (
  • The influence of age and Rhodococcus equi infection on CD1 expression by equine antigen presenting cells. (
  • Studies using antithymocyte globulin (ATG), and more recently the use of monoclonal antibodies to deplete T lymphocytes, revealed that contaminating mature T cells from the donor recognize the recipient's histocompatibility antigens. (
  • Stephanie Dougan received her PhD in immunology from Harvard University in 2007 after studying NKT cells and CD1d antigen presentation with Dr. Richard Blumberg. (
  • By harvesting as few as 200 primary lymphocytes from animals that are at the peak of an immune response, and by transfer of the nucleus from such antigen specific lymphocytes into an enucleated oocyte, embryonic stem cells that harbor the genetic rearrangements encoding the original antigen receptor may be obtained and used for the construction of transnuclear mice. (
  • The T cells are genetically modified through transduction with a retroviral vector expressing CD1D-specific T cell receptor. (
  • in vitro expansion of iNKT cells to antigen-pulsed autologous monocytes and recombinant CD1d/antigen coated beads was compared to differentiate inherent iNKT cell defects from defects in antigen presentation. (
  • Results The clonal repertoire of iNKT cells in healthy controls shows a broad distribution with regard to iNKT receptor affinity for CD1d. (
  • CD1d expression on antigen-presenting cells was not different between groups. (
  • iNKT cells in all early RA patients exhibited a bias in cytokine secretion towards Th1 cytokines, independent of CD1 antigen processing. (
  • The CD1d-tetramer + TCRβ + population was gated following stimulation with α-GalCer and induction of IL-4 (bottom right) or IFN-γ (bottom left) by NKT cells was assessed by flow cytometry. (
  • Human CD1D / R3G1 derived in Human Cells. (
  • 28 Furthermore 2 viral modulators of immune response (vMIRs) act as E3 ubiquitin ligases and down-regulate MHC-I. 29 , 30 vMIR2 also down-regulates ICAM-1 and CD86 by enhancing endocytosis, lysosomal targeting, and proteasome-mediated degradation 31 , 32 and increases endocytosis of CD1d, leading to the escape of infected cells from NKT cells. (
  • Disruption of a CD1d-mediated interaction between mast cells and NKT cells aggravates atherosclerosis. (
  • α-GalCer is a potent activator of iNKT cells, and a model CD1d antigen. (
  • Unlike MHC class I molecules that present peptide antigens, CD1d presents lipid antigens to natural killer T (NKT) cells. (
  • The cells are modified by adding a natural killer t-cell ligand, which permits them to stimulate natural killer T-cells, along with an antigen associated with a cancer. (
  • Tests in mice showed, moreover, that aggressive tumors could be shrunken by vaccinating the animals with aAVC cells that were programmed to display OVA antigen. (
  • aAVC are established using allogeneic cells (NIH3T3 or HEK293 cells for mice and humans, respectively) as vector cells by loading with NKT ligand, α-GalCerand co-electroporation with target Ag and CD1d mRNA. (
  • The closely-aggregated structures composed of CD11c+ DCs (green) and antigen-specific CD8+ T cells (red) around the vessels (blue) were seen in tumor sites. (
  • galactosyl ceramide is the prototypical ligand of CD1d, its activation of iNKT cells produces a mixture of T\(_H\)1 and T\(_H\)2 cytokines, which limits its therapeutic application. (
  • CD1 proteins constitute a family of antigen-presenting molecules ( 1 ), similar in structure to MHC class I antigen-presenting molecules. (
  • During the development of immune responses BCR-mediated uptake of antigen allows for its concentration and delivery to specialized late endosomes containing newly synthesized MHC class II molecules ( 7 ). (
  • The human CD1 gene family is composed of five nonpolymorphic genes ( CD1A , CD1B , CD1C , CD1D , and CD1E ) ( 9 ), whereas mice express only CD1d molecules. (
  • The CD1 family of major histocompatibility complex (MHC)-like molecules specializes in presenting lipid and glycolipid antigens to alpha/beta T lymphocytes, but little is known about the size of the CD1-restricted T cell population or the frequency of T lymphocytes specific for a given glycolipid antigen. (
  • CD1d molecules are noncovalently associated with β 2 -microglobulin to form a heterodimeric three-dimensional structure that is similar to the MHC class I molecules ( 1 ). (
  • CD1d is also expressed on immature cortical thymocytes and down-regulated on mature thymocytes in parallel with the expression of group I CD1 molecules ( 17 , 18 , 19 ). (
  • These observations strongly suggested that the phenotype observed in NPC2-deficient animals was directly linked to the efficiency of the loading of iGb3 into CD1d molecules expressed by thymocytes. (
  • Lipid transfer proteins, such as molecules of the saposin family, facilitate extraction of lipids from biological membranes for their loading onto CD1d molecules. (
  • In addition, it is unclear whether saposins, in addition to loading, also promote dissociation of lipids bound to CD1d molecules. (
  • Finally, using BIAcore assays we demonstrated that lipid-loaded saposin B increases the off-rate of lipids bound to CD1d molecules, providing important insights into the mechanisms by which it acts as a "lipid editor," capable of fine-tuning loading and unloading of CD1d molecules. (
  • By using superresolution microscopy, we show that CD1d molecules form nanoclusters at the cell surface of APCs, and their size and density are constrained by the actin cytoskeleton. (
  • CD1d is the only member of the group 2 CD1 molecules. (
  • Thus, while αβ TCR interact with peptides bound to MHC class I or class II molecules, γδ TCR recognize a diverse array of self and non-self antigens, such as small peptides, soluble or membrane proteins, phospholipids, prenyl pyrophosphates, and sulfatides. (
  • In contrast to antibodies, which recognize antigens in native form, αβ T cell receptors (TCRs) only recognize antigens as peptide fragments bound to MHC molecules, a feature known as MHC restriction. (
  • However, the discovery of MHC-class-I-like CD1 antigen-presentation molecules now explains how the immune system also recognizes the abundant and diverse universe of lipid-containing antigens. (
  • The CD1 molecules bind and present amphipathic lipid antigens for recognition by T-cell receptors. (
  • Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules. (
  • F, addition of anti-GD3 mAb to tumor-associated ascites restores NKT cell recognition of CD1d molecules. (
  • Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors. (
  • Hayday, A. C. & Vantourout, P. The innate biologies of adaptive antigen receptors. (
  • Humans express five family members (CD1a-e) that can be grouped into three groups based on sequence similarity: group 1 (CD1a-c), group 2 (CD1d), and group 3 (CD1e) ( 5 , 6 ). (
  • Crystal structures of human CD1a, b, and d, as well as mouse CD1d, without loading specific antigens, or in complex with different glycolipids or lipopeptides, have been extensively reviewed elsewhere ( 7 ⇓ ⇓ - 10 ). (
  • Mammalian CD1 proteins segregate into group I (CD1a, CD1b, and CD1c) and group II (CD1d) based on sequence homologies ( 1 , 2 ). (
  • Here we show that the mouse and human CD1d present glycolipids having different fatty acids, based in part upon a difference at a single amino acid position that is involved in positioning the sugar epitope. (
  • Recently, a different category of glycolipids, α-galactosyl diacylglycerolipids (α-GalDAG), have been identified as novel iNKT cell antigens. (
  • The Th1-biasing glycolipids have been found to consistently form complexes with CD1d that preferentially localize to plasma membrane cholesterol rich microdomains (lipid rafts), whereas CD1d complexes formed with Th2-biasing ligands are excluded from these microdomains. (
  • These data highlight the in vivo relevance of adding aromatic moieties to the 6''-OH position of the sugar and additionally show that judiciously chosen linkers are a promising strategy to generate strong Th1-polarizing glycolipids through increased binding either to CD1d or to NKTCR. (
  • Thus, the loading of endogenous and exogenous lipids and glycolipids onto CD1d is dependent on various small, soluble lipid transfer proteins present in the lysosome. (
  • The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). (
  • This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. (
  • Figure 1: Differences in the recognition of CD1d by type II NKT cell TCRs and type I i NKT cell TCRs. (
  • Additional reported applications (for the relevant formats) include: ELISA 1 , immunofluorescence 2 to detect CD1d in the lipid rafts on the cell membrane, and block 1 CD1d recognition of an i NKT cell hybridoma. (
  • Tumors frequently alter antigen processing and presentation by major histocompatibility complex (MHC) proteins in order to evade recognition by the immune system. (
  • Is the Subject Area "Antigen processing and recognition" applicable to this article? (
  • Recognition was not dependent upon an endosomal targeting motif in the cytoplasmic tail of CD1d. (
  • CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. (
  • In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo . (
  • The invariant T cell receptor of the iNKT cell is able to bind the CD1d:glycolipid complex leading to iNKT cell activation in both mice and humans. (
  • The CD1d gene encodes a divergent member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. (
  • We have shown in vitro and in vivo that iGb3 could not load CD1d spontaneously but rather required the assistance of lipid transfer proteins (LTPs) such as saposin ( 10 ). (
  • 11 ⇓ - 13 EBV modulates cellular antiviral responses in various ways, including down-regulation of major histocompatibility complex (MHC) proteins 14 and blocking proteasomal degradation and antigen synthesis. (
  • Antigen loading occurs in the endoplasmic reticulum with the help of chaperone proteins such as calreticulin. (
  • In this study, we report the identification of a membrane-associated protein, Ig-like transcript 4 (ILT4), as a novel human CD1d receptor that inhibits CD1d-mediated immune responses. (
  • The vector of anti-CD1D T cell receptor (TCR) is constructed for the engineering of T cell to target Human CD1D. (
  • Overall, these results define a previously unidentified mechanism that modulates iNKT cell autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d nanoclusters. (
  • Such antigens may be endogenous, derived from bacteria (foreign) and synthetic, the latter have been developed for clinical applications. (
  • B lymphocytes secrete antibody, present antigen and regulate immune responses. (
  • As antibodies are designed to specifically recognize and eliminate invading antigens, they are effective weapons used by the immune system to combat infection. (
  • Mice express only CD1d. (
  • Despite adequate surface CD1d expression and the presence of Ii, these mutant mice showed multiple and selective abnormalities in intracellular trafficking, antigen presentation and T cell development, demonstrating the critical functions of the CD1d cytoplasmic tail motif in vivo. (
  • Transfer of APCs presenting these "stabilized" CD1d/αGC complexes into mice resulted in immune responses with a more prominent Th1-like bias, characterized by increased NK cell transactivation and interferon-γ production. (
  • BALB/c-congenic mice harboring this null mutation of the CD1 antigen complex are described and available from The Jackson Laboratory Repository as Stock No. 003814 . (
  • Compared with wild-type mice, iNKT cell-deficient animals such as Jα18-knockout (KO) or CD1d-KO mice exhibited higher proinflammatory responses and exacerbated insulin resistance upon high-fat diet (HFD) ( 13 - 17 ). (
  • Accordingly, we generated adipocyte-specific CD1d-KO (CD1d ADKO ) mice and then analyzed the effects of adipocyte CD1d deletion on adipose tissue immune responses and metabolic alterations following HFD feeding. (
  • ApoE-/- mice crossed with CD1d-/- (CD1d-/-apoE-/-) mice exhibited a 25% decrease in lesion size compared with apoE-/- mice. (
  • 5-wk-old female apoE−/− and apoE−/−CD1d−/− mice were injected twice a week for 10 wk with αGalCer or PBS and killed 48 h after the last injection (n = 12 for each group). (
  • b) Lesion size at every 100 μm for the first 600 μm of the aortic root in apoE−/− and apoE−/−CD1d−/− mice. (
  • In apoE−/− CD1d−/− mice, αGalCer did not affect lesion size (Fig. 1, a and c), demonstrating that the effect of αGalCer on atherosclerosis depends on CD1d. (
  • We also use the technology in reverse to clone mice from tumor-infiltrating Tregs as a means of determining their antigen-specificity. (
  • To find whether it worked in actual bodies, they conducted experiments in mice with a virulent form of melanoma that also expresses a model antigen called OVA. (
  • C57BL/6, BALB/c, cd1d -null, and rag1 -null mice were purchased from Jackson Laboratory (Bar Harbor, ME). (
  • Cd1d -null mice were backcrossed onto the BALB/c background for at least 10 generations. (
  • There are currently no images for CD1.1 antigen Antibody (NBP1-28362). (
  • The conservation of this cell population and of the CD1d ligand across species indicates an important immunological function. (
  • Given the importance of human immune responses, we conducted a human-mouse cross-species analysis of iNKT-cell activation by iGb3-CD1d. (
  • Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. (
  • CD1d also can bind nonantigenic lipids, however, but unexpectedly, mouse CD1d orients the two aliphatic chains of a nonantigenic lipid rotated 180°, causing a dramatic repositioning of the exposed sugar. (
  • Importantly, we determined that similar to saposins, recombinant NPC2 was able to unload lipids from and load lipids into CD1d. (
  • C57BL/6 mouse splenocytes were stained purified CD1d (clone K253, filled histogram) or mouse IgG1 isotype control, followed by anti-mouse IgG1 PE. (
  • Understanding the transcriptional control mechanism would help to reveal how the CD1d expression is regulated in NK T cell-associated immune responses. (
  • CD1d is also known as R3G1 Some of the known ligands for CD1d are: α-galactosylceramide (α-GalCer), a compound originally derived from the marine sponge Agelas mauritanius with no physiological role but great research utility. (
  • The development of MHC multimer technology has provided a breakthrough in the ability to follow T cell populations defined by their antigen specificity ( 28 )( 29 ). (
  • Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. (
  • CD1d is a 49 kDa heavy chain associated with Beta 2 microglobulin on cortical thymocytes. (
  • Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton and correlates with enhanced iNKT cell activation. (
  • We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. (
  • In combination with a peptide antigen, α-GalCer is able to stimulate a strong immune response against the epitope. (
  • The analysis of the CD1D promoter region indicates that IFN-γ, NF-IL-6, and T cell factor 1/lymphoid enhancer-binding factor 1 are most likely involved in the regulation of CD1d expression. (
  • However, NK T cell reactivity to CD1d is greatly augmented by the glycosphingolipid α-galactosylceramide (α-GalCer) ( 16 ), obtained from an extract of the marine sponge Agelas mauritanius . (
  • These findings support a model in which low endosomal pH controls stability and lipid raft localization of CD1d-glycolipid complexes to regulate the outcome of iNKT cell mediated responses. (
  • This selection process requires the intracellular trafficking of CD1d to late endosomal and lysosomal compartments ( 14 ). (
  • Signal transducer CD24 also known as cluster of differentiation 24 or heat stable antigen CD24 (HSA) is a protein that in humans is encoded by the CD24 gene. (
  • It is unclear whether the difference in CD1d expression between individuals is due to their genetic variation or an environmental stimulation or both. (
  • iGb3, a self antigen which has been implied in iNKT selection. (
  • In contrast, treatment with the more selective HDACi, MC1568, resulted in an increase in CD1d-mediated NKT cell activation, but did not enhance antigen presentation by HLA-DR4. (
  • B cell activation and antibody production against foreign antigens is a central step of host defense. (
  • Upon activation by anti-CD3 or CD1d, the clones produced both Th1 and Th2 cytokines. (
  • Ganglioside treatment alters CD1d-mediated NKT cell activation. (
  • Pretreatment with the indicated purified gangliosides altered CD1d-mediated NKT cell activation. (
  • In contrast with previous BIAcore-based estimates of very short half-lives for CD1d-glycolipid complexes, we found that the dissociation rate of several different CD1d-glycolipid complexes was very slow. (
  • CD1d is a type I transmembrane protein and member of the MHC family, with a molecular weight ranging from 43-49 kD, depending on the glycosylation degree. (
  • CD1d is a MHC-like, type I transmembrane protein, member of the CD1 family and the immunoglobulin superfamily. (
  • Molecular identification of tumor-associated antigens not only provided the means to activate or monitor anti-tumor immunity, but also gave insights. (
  • Alterations in the lipid tails or other portions of CD1d-presented glycolipid ligands can bias the iNKT response towards production of predominantly Th1 or Th2 associated cytokines. (
  • Yuan W, Kang SJ, Evans JE, Cresswell P (2009) Natural lipid ligands associated with human CD1d targeted to different subcellular compartments. (
  • Little is known about the intracellular pathways of CD1 trafficking and antigen presentation. (