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).

The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23. (1/302)

The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.  (+info)

The thrombospondin receptor integrin-associated protein (CD47) functionally couples to heterotrimeric Gi. (2/302)

Integrin-associated protein (IAP; CD47) is a thrombospondin receptor that forms a signaling complex with beta3 integrins resulting in enhanced alphavbeta3-dependent cell spreading and chemotaxis and, in platelets, alphaIIbbeta3-dependent spreading and aggregation. These actions of CD47 are all specifically abrogated by pertussis toxin treatment of cells. Here we report that CD47, its beta3 integrin partner, and Gi proteins form a stable, detergent-soluble complex that can be recovered by immunoprecipitation and affinity chromatography. Gialpha is released from this complex by treatment with GTP or AlF4. GTP and AlF4 also reduce the binding of CD47 to its agonist peptide (4N1K) derived from thrombospondin, indicating a direct association of CD47 with Gi. 4N1K peptide causes a rapid decrease in intraplatelet cyclic AMP levels, a Gi-dependent event necessary for aggregation. Finally, 4N1K stimulates the binding of GTPgamma35S to membranes from cells expressing IAP and alphavbeta3. This functional coupling of CD47 to heterotrimeric G proteins provides a mechanistic explanation for the biological effects of CD47 in a wide variety of systems.  (+info)

Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome is mediated by beta3 integrins. (3/302)

Hantaviruses replicate primarily in the vascular endothelium and cause two human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). In this report, we demonstrate that the cellular entry of HFRS-associated hantaviruses is facilitated by specific integrins expressed on platelets, endothelial cells, and macrophages. Infection of human umbilical vein endothelial cells and Vero E6 cells by the HFRS-causing hantaviruses Hantaan (HTN), Seoul (SEO), and Puumala (PUU) is inhibited by antibodies to alphavbeta3 integrins and by the integrin ligand vitronectin. The cellular entry of HTN, SEO, and PUU viruses, but not the nonpathogenic Prospect Hill (PH) hantavirus (i.e., a virus with no associated human disease), was also mediated by introducting recombinant alphaIIbbeta3 or alphavbeta3 integrins into beta3-integrin-deficient CHO cells. In addition, PH infectivity was not inhibited by alphavbeta3-specific sera or vitronectin but was blocked by alpha5beta1-specific sera and the integrin ligand fibronectin. RGD tripeptides, which are required for many integrin-ligand interactions, are absent from all hantavirus G1 and G2 surface glycoproteins, and GRGDSP peptides did not inhibit hantavirus infectivity. Further, a mouse-human hybrid beta3 integrin-specific Fab fragment, c7E3 (ReoPro), also inhibited the infectivity of HTN, SEO, and PUU as well as HPS-associated hantaviruses, Sin Nombre (SN) and New York-1 (NY-1). These findings indicate that pathogenic HPS- and HFRS-causing hantaviruses enter cells via beta3 integrins, which are present on the surfaces of platelets, endothelial cells, and macrophages. Since beta3 integrins regulate vascular permeability and platelet function, these findings also correlate beta3 integrin usage with common elements of hantavirus pathogenesis.  (+info)

Cell spreading distinguishes the mechanism of augmentation of T cell activation by integrin-associated protein/CD47 and CD28. (4/302)

Integrin-associated protein (IAP/CD47) is a 50 kDa transmembrane protein initially defined as a regulator of beta3 integrin-mediated functions in neutrophils. IAP also can synergize with the TCR in T cell activation independent of beta3 integrins. To analyze the mechanism for IAP synergy with TCR, we expressed in Jurkat cells a chimeric molecule, consisting of the CD16 extracellular domain, the CD7 transmembrane domain and the TCR zeta chain cytoplasmic tail (CD16-7-zeta), which on its own is unable to induce IL-2 production. Ligation of IAP acted in synergy with TCR to induce IL-2 transcription and synthesis, but failed to synergize with the signal generated by CD16-7-zeta, while CD28 was a potent co-stimulator with both TCR and CD16-7-zeta. The failure of IAP to activate Jurkat together with CD16-7-zeta correlated with a lack of c-Jun N-terminal kinase, but not extracellular-signal-regulated kinase activation. Jurkat adhesion to anti-IAP, but not anti-CD28, induced cell spreading and the same domains of IAP required for augmentation of T cell activation were required to induce cell spreading. IAP synergy with TCR signaling likely results from its ability to stimulate adhesion to a ligand-expressing surface or antigen-presenting cell (APC), rather than from initiation of a novel signaling cascade. We conclude that a major role for ligation of IAP in T cell activation is to enhance the efficiency of TCR signaling by causing T cells to spread on an APC or surface.  (+info)

CD47 signals T cell death. (5/302)

Activation-induced death of T cells regulates immune responses and is considered to involve apoptosis induced by ligation of Fas and TNF receptors. The role of other receptors in signaling T cell death is less clear. In this study we demonstrate that activation of specific epitopes on the Ig variable domain of CD47 rapidly induces apoptosis of T cells. A new mAb, Ad22, to this site induces apoptosis of Jurkat cells and CD3epsilon-stimulated PBMC, as determined by morphological changes, phosphatidylserine exposure on the cell surface, uptake of propidium iodide, and true counts by flow cytometry. In contrast, apoptosis was not observed following culture with anti-CD47 mAbs 2D3 or B6H12 directed to a distant or closely adjacent region, respectively. CD47-mediated cell death was independent of CD3, CD4, CD45, or p56lck involvement as demonstrated by studies with variant Jurkat cell lines deficient in these signaling pathways. However, coligation of CD3epsilon and CD47 enhanced phosphatidylserine externalization on Jurkat cells with functional CD3. Furthermore, normal T cells required preactivation to respond with CD47-induced apoptosis. CD47-mediated cell death appeared to proceed independent of Fas or TNF receptor signaling and did not involve characteristic DNA fragmentation or requirement for IL-1beta-converting enzyme-like proteases or CPP32. Taken together, our data demonstrate that under appropriate conditions, CD47 activation results in very rapid T cell death, apparently mediated by a novel apoptotic pathway. Thus, CD47 may be critically involved in controlling the fate of activated T cells.  (+info)

Thrombospondin-1 acts via IAP/CD47 to synergize with collagen in alpha2beta1-mediated platelet activation. (6/302)

Integrin-associated protein (IAP; or CD47) is a receptor for the cell binding domain (CBD) of thrombospondin-1 (TS1). In platelets, IAP associates with and regulates the function of alphaIIbbeta3 integrin (Chung et al, J Biol Chem 272:14740, 1997). We test here the possibility that CD47 may also modulate the function of platelet integrin alpha2beta1, a collagen receptor. The CD47 agonist peptide, 4N1K (KRFYVVMWKK), derived from the CBD, synergizes with soluble collagen in aggregating platelet-rich plasma. 4N1K and intact TS1 also induce the aggregation of washed, unstirred platelets on immobilized collagen with a rapid increase in tyrosine phosphorylation. The effects of TS1 and 4N1K on platelet aggregation are absolutely dependent on IAP, as shown by the use of platelets from IAP-/- mice. Prostaglandin E1 (PGE1) prevents 4N1K-dependent aggregation on immobilized collagen but does not inhibit the 4N1K peptide stimulation of alpha2beta1-dependent platelet spreading. Finally, a detergent-stable, physical association of IAP and alpha2beta1 integrin is detected by coimmunoprecipitation. These results imply a role for IAP and TS1 in the early activation of platelets upon adhesion to collagen.  (+info)

Role of cholesterol in formation and function of a signaling complex involving alphavbeta3, integrin-associated protein (CD47), and heterotrimeric G proteins. (7/302)

Integrin-associated protein (CD47) is a multiply membrane spanning member of the immunoglobulin superfamily that regulates some adhesion-dependent cell functions through formation of a complex with alphavbeta3 integrin and trimeric G proteins. Cholesterol is critical for the association of the three protein components of the supramolecular complex and for its signaling. The multiply membrane spanning domain of IAP is required for complex formation because it binds cholesterol. The supramolecular complex forms preferentially in glycosphingolipid-enriched membrane domains. Binding of mAb 10G2 to the IAP Ig domain, previously shown to be required for association with alphavbeta3, is affected by both the multiply membrane spanning domain and cholesterol. These data demonstrate that cholesterol is an essential component of the alphavbeta3/IAP/G protein signaling complex, presumably acting through an effect on IAP conformation.  (+info)

Identification of CD47/integrin-associated protein and alpha(v)beta3 as two receptors for the alpha3(IV) chain of type IV collagen on tumor cells. (8/302)

Previous studies from our laboratories demonstrated that a peptide from the noncollagenous domain of the alpha3 chain of basement membrane collagen (COL IV), comprising residues 185-203, inhibits polymorphonuclear leukocyte activation and melanoma cell proliferation independently of its ability to promote cell adhesion; these properties require the presence of the triplet -SNS- at residues 189-191 (J. C. Monboisse et al., J. Biol. Chem., 269: 25475-25482, 1994; J. Han et al., J. Biol. Chem., 272: 20395-20401, 1997). More recently, we demonstrated that native COL IV and -SNS-containing synthetic peptides (10 microg/ml) added to culture medium inhibit the proliferation of not only melanoma cells but also breast, pancreas, and stomach tumor cells up to 82% and prostate tumor cells by 15%. This inhibition was shown to be dependent on a COL IV- or peptide-induced increase in intracellular cAMP (T. A. Shahan et al., Connect. Tissue Res., 40: 221-232, 1999). Attempts to identify the putative receptor(s) on tumor cells led to the isolation of five proteins (Mr 33,000, 52,000, 72,000, 95,000, and 250,000) from melanoma and prostate cells by affinity purification with the alpha3(IV)179-208 peptide. The Mr 52,000, 95,000, and 250,000 proteins were shown to be CD47/integrin-associated protein(IAP), the integrin beta3 subunit, and the alpha(v)beta3 integrin complex, respectively. The Mr 33,000 and 72,000 proteins have not yet been identified. To confirm the specificity of ligand binding to the receptors, cell membranes from either melanoma or prostate tumor cells were pretreated with the unlabeled ligand alpha3(IV)187-191 (-YYSNS-); alternatively, the peptide was pretreated with a peptide-reactive monoclonal antibody (A5D7) before receptor isolation. These treatments inhibited the purification of CD47/IAP, the integrin beta3 subunit, and the alpha(v)beta3 integrin complex from tumor cells. Furthermore, cells treated with CD47/IAP- or the alpha(v)beta3 integrin-reactive antibodies prevented the alpha3(IV)185-203 peptide from inhibiting cell proliferation and the subsequent rise in intracellular cAMP. Pretreating cells with the alpha3(IV)187-191 (-YYSNS-) peptide also inhibited their adhesion to the alpha3(IV)185-203 peptide substrate, whereas the inactive alpha1(IV)185-203 peptide, from the same region of the alpha1 chain as the alpha3(IV)185-203 peptide, had no effect. Incubation of cells with either CD47/IAP and/or alpha(v)beta3 integrin-reactive antibodies inhibited their adhesion to the alpha3(IV)185-203 peptide, whereas antibodies to the beta1 and beta2 integrin subunits were without effect. These data suggest that ALC-COL IV, through its alpha3(IV) chain, inhibits tumor cell proliferation using the receptors CD47/IAP and the alpha(v)beta3 integrin.  (+info)

Two closely related proteins, signal regulatory protein α (SIRPα; SHPS-1/CD172) and SIRPβ, have been described in humans. The existence of a third SIRP protein has been suggested by cDNA sequence only. We show that this third SIRP is a separate gene that is expressed as a protein with unique characteristics from both α and β genes and suggest that this gene should be termed SIRPγ. We have expressed the extracellular region of SIRPγ as a soluble protein and have shown that, like SIRPα, it binds CD47, but with a lower affinity (K d , ∼23 μM) compared with SIRPα (K d , ∼2 μM). mAbs specific to SIRPγ show that it was not expressed on myeloid cells, in contrast to SIRPα and -β, being expressed instead on the majority of T cells and a proportion of B cells. The short cytoplasmic tail of SIRPγ does not contain any known signaling motifs, nor does it contain a characteristic lysine, as with SIRPα, that is required for DAP12 interaction. DAP12 coexpression is a requirement for SIRPβ surface
Complete information for SIRPA gene (Protein Coding), Signal Regulatory Protein Alpha, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Neutrophil granulocytes constitute the front line of defense in the innate immune response to invading microorganisms, but can also contribute to development of inflammatory disease and tissue destruction following e.g. myocardial infarction or stroke. During inflammatory activation, neutrophils leave the blood, interact with extracellular matrix proteins, and migrate into tissues in response to chemotactic factors to phagocytose and kill infectious agents by using toxic granule contents and reactive oxygen metabolites. The functional neutrophil response relies on exocytosis of cytoplasmic granules, each containing membrane proteins, which are thereby mobilized to the plasma membrane. Specific programmed cell death (apoptotic) pathways regulate neutrophil homeostasis, where an inflammatory milieu can prolong the life span of neutrophils to several days, whereas non-activated neutrophils are committed to constitutive/spontaneous apoptosis within hours.. Signal regulatory protein alpha (SIRPα) is ...
Signal-regulatory protein alpha (SIRPalpha) is a myeloid membrane receptor that interacts with the membrane protein CD47, a marker of self. We have solved the structure of the complete extracellular portion of SIRPalpha, comprising three immunoglobulin superfamily domains, by x-ray crystallography to 2.5 A resolution. These data, together with previous data on the N-terminal domain and its ligand CD47 (possessing a single immunoglobulin superfamily domain), show that the CD47-SIRPalpha interaction will span a distance of around 14 nm between interacting cells, comparable with that of an immunological synapse. The N-terminal (V-set) domain mediates binding to CD47, and the two others are found to be constant (C1-set) domains. C1-set domains are restricted to proteins involved in vertebrate antigen recognition: T cell antigen receptors, immunoglobulins, major histocompatibility complex antigens, tapasin, and beta2-microglobulin. The domains of SIRPalpha (domains 2 and 3) are structurally more similar to
CD47 functions as a marker of self on red blood cells (RBCs) by binding to signal regulatory protein alpha on macrophages, preventing phagocytosis of autologous RBCs by splenic red pulp macrophages, and Fcgamma receptor (FcgammaR)- or complement receptor-mediated phagocytosis by macrophages in general. RBC senescence involves a series of biochemical changes to plasma membrane proteins or lipids, which may regulate phagocytosis by macrophages. Here, we investigated whether CD47 on experimentally senescent murine RBCs affects their phagocytosis by macrophages in vitro. Clustering of CD47 with antibodies was more pronounced in the plasma membrane of untreated RBCs, compared with that in in vitro oxidized RBCs (Ox-RBCs). Phagocytosis of Ox-RBCs was mediated by scavenger receptors (SRs) distinct from SR-A or CD36 and required serum factors. We found that wild-type (WT) and CD47(-/-) Ox-RBCs were phagocytosed equally well by macrophages in the presence of serum, suggesting that phagocytosis via SRs is ...
Clone REA479 recognizes the human CD172g antigen, a single-pass type I membrane protein also known as signal-regulatory protein γ (SIRPγ) or signal-regulatory protein β 2 (SIRPβ2). Signal regulatory proteins (SIRPs) are a family of transmembrane receptor-like signaling proteins that are abundantly expressed in hematopoietic cells, including granulocytes, monocytes, dendritic cells, and lymphocytes. In addition, SIRPs are expressed in neuronal cells and certain types of cancer cells. CD172g is the only member of the SIRP family that is expressed on T cells, some B cells, CD56bright natural killer (NK) cells, and all activated NK cells. CD172g does bind CD47, albeit with less affinity than CD172a (SIRPα). This interaction mediates cell-cell adhesion, rather than inhibitory signals. The adhesion mediated by contact of CD172g on T cells with CD47 on antigen-presenting cells (APCs) promotes antigen-specific T cell proliferation and costimulates T cell activation.Additional information: Clone REA479
TY - JOUR. T1 - Integrin-associated protein. T2 - A 50-kD plasma membrane antigen physically and functionally associated with integrins. AU - Brown, Eric. AU - Hooper, Lora. AU - Ho, Thang. AU - Gresham, Hattie. PY - 1990/12/1. Y1 - 1990/12/1. N2 - Phagocytosis by monocytes or neutrophils can be enhanced by interaction with several proteins or synthetic peptides containing the Arg-Gly-Asp sequence. Recently we showed that an mAb, B6H12, specifically inhibited this enhancement of neutrophi1 phagocytosis by inhibiting Arg-Gly-Asp binding to the leukocyte response integrin (Gresham, H.D., J.L. Goodwin, P.M. Allen, D.C. Anderson, and E.J. Brown. 1989. J. Cell Biol. 108:1935-1943). Now, we have purified the antigen recognized by B6H12 to homogeneity. Surprisingly, it is a 50-kD molecu1e that is expressed on the plasma membranes of all hematopoietic cells, including erythrocytes, which express no known integrins. On platelets and placenta, but not on erythrocytes, this protein is associated with an ...
CD47 is a widely distributed membrane protein that interacts with signal-regulatory protein α (SIRPα), an inhibitory receptor on myeloid cells that gives a dont-eat-me signal. Manipulation of the interaction is of considerable interest in the immunotherapy of cancer and in xenotransplantation. The amino-terminal ligand binding domain of SIRPα is highly polymorphic in contrast to the single Ig-like domain of CD47. There is confusion as to whether the polymorphisms will affect ligand binding, but this is an important point for this interaction and other paired receptors being considered as targets for therapy. We show by x-ray crystallography that one human SIRPα allele differing in 13 amino acid residues has a very similar binding site and that several different alleles all bind CD47 with similar affinity as expected because the residues are mostly surface-exposed and distant from the binding site. A peptide from the binding site of CD47 has been reported to mimic the CD47 interaction with SIRPα,
Clone REA1170 recognizes the human CD172b antigen, a single-pass type I membrane protein also known as signal-regulatory protein beta (SIRPβ). Signal regulatory proteins (SIRPs) are a family of transmembrane receptor-like signaling proteins that are abundantly expressed in hematopoietic cells, including granulocytes, monocytes, dendritic cells, and lymphocytes. In addition, SIRPs are expressed in neuronal cells and certain types of cancer cells. SIRPs can be divided into two subfamilies, CD172a and CD172b, based on the putative structures of their C-terminal intracellular domains which distinguish them as either activating (CD172b) or inhibitory (CD172a) isoforms. CD172b is expressed on peripheral blood monocytes, dendritic cells, and granulocytes.Additional information: Clone REA1170 displays negligible binding to Fc receptors. - Norge
Interaction of signal regulatory protein (SIRP) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRP enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitts lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) invitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (NOD)/SCID mice. However, the effects of blocking Abs to human SIRP in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous SIRP expressed on macrophages of immunodeficient mice. With the use of Rag2(c)(-/-)(-/-) mice harboring a transgene for human SIRP under the control of human regulatory elements (hSIRP-DKO mice), we here show that a blocking Ab to human SIRP significantly enhanced the ADCP activity of ...
Signal-regulatory protein beta 1a (SIRP beta 1a) is a disulfide-linked type I membrane glycoprotein that belongs to the SIRP/SHPS (CD172) family of the immunoglobulin (Ig) superfamily. The SIRP family are paired receptors that have similar extracellular domains but differing C-terminal domains and functions (1). Members of this family are characterized by an extracellular region containing a V-set Ig domain containing a J-like sequence and two C1-set Ig domains. Positively charged residues within the transmembrane domain mediate interactions with DAP12 proteins which contain immunoreceptor tyrosine-based activation motifs (ITAMs) (3). Proteins in the SIRP family are typically expressed in cells of monocyte, macrophage or dendritic lineages (4). Mouse SIRP beta 1a shares 57% and 59% amino acid sequence identity with human SIRP beta 1 and rat SIRP alpha, respectively. SIRP beta 1 has a relatively short cytoplasmic region and lacks the signaling motifs for association with phosphatases. However, ...
Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton. Upon Fc receptor activation, Src-family kinase signaling leads to segregation of FcγRI and SIRPα nanoclusters to be 197 ± 3 nm apart. Co-ligation of SIRPα with CD47 abrogates nanocluster segregation. If the balance of signals favors activation, FcγRI nanoclusters reorganize into periodically spaced concentric rings. Thus, a nanometer- and micron-scale reorganization of activating and inhibitory
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The P84 monoclonal antibody reacts with Signal-Regulatory Protein α (SIRPα), also known as CD172a. SIRPα is a type I transmembrane glycoprotein expressed on monocytes, macrophages, and dendritic cells. Neurons and other tissues of the central nervous system have also been shown to express SIRPα. Its ligand, CD47 is expressed by a wide variety of cells. SIRPα and CD47 regulate dendritic cell-mediated T cell activation, neutrophil migration, and phagocytosis. SIRPα diffuses laterally on the macrophage membrane and accumulates at a phagocytic synapse to bind CD47 which inhibits phagocytosis by macrophages. Anti-SIRPα antibodies that block the interaction of SIRPα with CD47 have been shown to suppress tumor formation in mice. The P84 antibody has been shown to have neutralizing activity in vivo and in vitro ...
Activation of the mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) cascades after Toll-like receptor (TLR) stimulation contributes to innate immune responses. Signal regulatory protein (SIRP) α, a member of the SIRP family that is abundantly expressed in macrophages, has been implicated in regulating MAPK and NF-κB signaling pathways. In addition, SIRPα can negatively regulate the phagocytosis of host cells by macrophages, indicating an inhibitory role of SIRPα in innate immunity. We provide evidences that SIRPα is an essential endogenous regulator of the innate immune activation upon lipopolysaccharide (LPS) exposure. SIRPα expression was promptly reduced in macrophages after LPS stimulation. The decrease in SIRPα expression levels was required for initiation of LPS-induced innate immune responses because overexpression of SIRPα reduced macrophage responses to LPS. Knockdown of SIRPα caused prolonged activation of MAPKs and NF-κB pathways and augmented ...
|span style=font-family:Times,serif;font-size:9pt;>The B4B6 monoclonal antibody specifically binds to CD172b, which is also known as Signal regulatory protein β (SIRPβ), or SIRP-beta-1 (SIRPB1/SIRP|/span>|span style=font-family:Arial,Helvetica,sans-serif;font-size:9pt;>β|/span>|span style=font-family:Times,serif;font-size:9pt;>1). CD172b is a 50 kDa, type I transmembrane glycoprotein that belongs to the SIRP family within the Ig gene superfamily. CD172b has a transmembrane domain that contains a positively-charged lysine residue. This allows CD172b to interact with a transmembrane signaling adaptor protein, DAP12/KARAP, and transduce stimulatory signals into cells. CD172b is expressed on monocytes, macrophages, dendritic cells, and granulocytes. It is not expressed on CD34+ cells. CD172b/SIRPβ and its counterpart, CD172a/SIRP|/span>|span style=font-family:Arial,Helvetica,sans-serif;font-size:9pt;>α|/span>|span style=font-family:Times,serif;font-size:9pt;>, appear to have complementary
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Immunoglobulin-like cell surface receptor involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes.
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Targeting the CD47-signal-regulatory protein α (SIRPα) pathway represents a novel therapeutic approach to enhance anti-cancer immunity by promoting both innate and adaptive immune responses. Unlike CD47, which is expressed ubiquitously, SIRPα expression is mainly restricted to myeloid cells and neurons. Therefore, compared to CD47-targeted therapies, targeting SIRPα may result in differential safety and efficacy profiles, potentially enabling lower effective doses and improved pharmacokinetics and pharmacodynamics. The development of effective SIRPα antagonists is restricted by polymorphisms within the CD47-binding domain of SIRPα, necessitating pan-allele reactive anti-SIRPα antibodies for therapeutic intervention in diverse patient populations. We immunized wild-type and human antibody transgenic chickens with a multi-allele and multi-species SIRPα regimen in order to discover pan-allelic and pan-mammalian reactive anti-SIRPα antibodies suitable for clinical translation. A total of ...
Menglan Xiang, Rubén Adrián Grosso, Akira Takeda, Junliang Pan, Tove Bekkhus, Kevin Brulois, Denis Dermadi, Sofia Nordling, Michael Vanlandewijck, Sirpa Jalkanen, Maria H. Ulvmar, Eugene C. ...
Kohtaamisia kasvatuksen ja koulutuksen kentillä. Erontekoja ja yhdessä tekemistä.. Mietola, Reetta, Lahelma, Elina, Lappalainen, Sirpa (toim). 2005. Kohtaamisia kasvatuksen ja koulutuksen kentillä. Erontekoja ja yhdessä tekemistä. Suomen Kasvatustieteellinen Seura. Julkaisuja No 22, 2005.. ...
CD47 (Cluster of Differentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD-47 acts as a dont eat me signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis. CD47 is involved in a range of cellular processes, including apoptosis, proliferation, adhesion, and migration. Furthermore, it plays a key role in immune and angiogenic responses. CD47 is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells. Expression in equine cutaneous tumors has been reported as well ...
CD47 (Cluster of Differentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD47 is involved in a range of cellular processes, including apoptosis, proliferation, adhesion, and migration. Furthermore, it plays a key role in immune and angiogenic responses. CD47 is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells.
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SIRPB1 - SIRPB1 (untagged)-Human signal-regulatory protein beta 1 (SIRPB1), transcript variant 2 available for purchase from OriGene - Your Gene Company.
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High autophagic activity in podocytes, terminally differentiated cells that serve as main components of the kidney filtration barrier, is essential for podocyte survival under various challenges. How podocytes maintain such a high level of autophagy, however, remains unclear. Here we report that signal regulatory protein α (SIRPα) plays a key role in promoting podocyte autophagy. Unlike other glomerular cells, podocytes strongly expressed SIRPα, which was, however, downregulated in patients with focal segmental glomerulosclerosis and mice with experimental nephropathy. Podocyte SIRPα levels were inversely correlated with the severity of podocyte injury and proteinuria but positively with autophagy. Compared with WT littermates, Sirpa-deficient mice displayed greater age-related podocyte injury and proteinuria and developed more rapid and severe renal injury in various models of experimental nephropathy. Mechanistically, podocyte SIRPα strongly reduced Akt/GSK-3β/β-catenin signaling, ...
TY - JOUR. T1 - Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis. AU - Koh, Eunee. AU - Lee, Eun Jung. AU - Nam, Gi Hoon. AU - Hong, Yeonsun. AU - Cho, Eunji. AU - Yang, Yoosoo. AU - Kim, In-San. PY - 2017/3/1. Y1 - 2017/3/1. N2 - CD47, a dont eat me signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein α (SIRPα) on phagocytic cells. By engaging SIRPα, CD47 limits the ability of macrophages to engulf tumor cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to ...
Mesenteric lymph node (mLN) CD103 (αE integrin)+ dendritic cells (DCs) induce regulatory T cells and gut tolerance. However, the function of intestinal CD103− DCs remains to be clarified. CD47 is the ligand of signal regulatory protein α (SIRPα) and promotes SIRPα+ myeloid cell migration. We first show that mucosal CD103− DCs selectively express SIRPα and that their frequency was augmented in the lamina propria and mLNs of mice that developed Th17-biased colitis in response to trinitrobenzene sulfonic acid. In contrast, the percentage of SIRPα+CD103− DCs and Th17 responses were decreased in CD47-deficient (CD47 knockout [KO]) mice, which remained protected from colitis. We next demonstrate that transferring wild-type (WT), but not CD47 KO, SIRPα+CD103− DCs in CD47 KO mice elicited severe Th17-associated wasting disease. CD47 expression was required on the SIRPα+CD103− DCs for efficient trafficking to mLNs in vivo, whereas it was dispensable on both DCs and T cells for Th17 ...
Fab 218 anti-SIRP-alpha antibody Variable Heavy ChainFab 218 anti-SIRP-alpha antibody Variable Light ChainTyrosine-protein phosphatase non-receptor type substrate 1
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Protein tyrosine phosphatases (PTPases) SHP-1 and SHP-2 are critical regulators in the intracellular signaling pathways that result in cell responses such as mitosis, differentiation, migration, survival, transformation or death. SHP-2 is a signal transducer for several receptor tyrosine kinases and cytokine receptors. A novel SHP-2 associated glycoprotein was recently cloned from human, rat, mouse and cattle by several labs and was designated SIRPalpha, SHPS-1, MyD-1, BIT and p84. SIRPalpha is a new gene family containing at least fifteen members. SIRPalpha is a substrate of many activated tyrosine kinases such as insulin receptor, EGFR, PDGFR and src, and a specific docking protein for SHP-2. SIRPalpha has regulatory effects on cellular responses induced by serum, growth factors, insulin, oncogenes, growth hormones and cell adhesion and plays a general role in different physiological and pathological processes.. ...
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Sirpa: All the pens in this case are inked up and in use. (I actually have a few more that are not inked up and in use...) Ive found this is pretty much the maximum that I can keep in rotation, and I still get some ink drying issues when I neglect one particular pen. I try to rotate them all and use them all, and as theyre filled with mostly different inks, that usually works. But the quality of the pen and the quality of the ink make a big difference; some are reluctant to write without a little moistening after a week or so, whereas others can go for many weeks or months and then write beautifully, immediately. Keeping the pens well exercised and maintained is the key, and fountain pens DO need to be maintained. Its part of the loving ritual, I guess, and the tradeoff for all those fancy ink colors ...
Siinkohal on kohane kritiseerida ka valitsevat arvamust, nagu oleks kaalu langetamine imelihtne - tuleb vaid süüa vähem ja sportida rohkem. Paraku me kõik teame, et sellel on vaid lühiajaline mõju. Inimkeha on väga kohanemisvõimeline. Kui toidust saadav energiakogus väheneb, siis hakkab keha vastusena vähendama ka kulutatavat energiat - ainevahetuse baastase langeb. Seda on teatud tegelikult juba pea sada aastat14 ja see muudab meie praeguse obsessiivse kalorilugemismaania veelgi veidramaks. Dieeditav inimene tunneb ennast peagi apaatse ja väsinuna, tal on külm ja pidevalt vaevab näljatunne. Tõsi, kaal on vähenenud, aga peagi jõutakse nn platooni, mis tähendab seda, et kulutatav ja tarbitav energiakogus on tasakaalus.. Kui masenduses dieeditaja siis näljatunde leevendamiseks pisut rohkem sööma hakkab, hakkavad ka kilod tagasi tulema, sest ainevahetus on endiselt kokkuhoiurežiimil. Kõige kurvem on, et see juhtub ka siis, kui tarbitav energiakogus on ikkagi palju väiksem kui ...
During the development of multicellular organisms, integrins act through integrin-associated molecules to regulate essential aspects of cell-cell and cell-matrix adhesion, cell polarity and cell survival. On p. 2913, Reinhard Fässler and co-authors report that the integrin-associated protein PINCH1 regulates all four of these processes during the peri-implantation stage of mouse development. PINCH1 interacts with integrin cytoplasmic tails at focal adhesions via integrin-linked kinase (ILK). The authors show that, like β1-integrin- and Ilk-deficient mice, mouse embryos carrying a disrupted PINCH1 gene arrest at the peri-implantation stage. To pinpoint this phenotype, the authors examined embryoid bodies (EBs), an experimental model for this stage of development. Although PINCH1-null EBs show many of the same defects as β1-integrin- and Ilk-mutant EBs (including abnormal epiblast polarity and detachment of cells from matrix), they also exhibit abnormal cell-cell adhesion and increased ...
Sirpa Leppänens publications ...
Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr−/−) mice, CD11c+ MHCII+ DCs could be discriminated into CD103− CD11b+F4/80+, CD11b+F4/80− and CD11b−F4/80− DCs and CD103+ CD11b−F4/80− DCs. Except for CD103− CD11b− F4/80− DCs, these subsets expanded in high fat diet-fed Ldlr−/− mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103− CD11b− F4/80− but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l−/−) mice, a specific loss of CD103+ ...
SLC17A9, gene, SLC2A4RG, SLA2, SIRPB1, Signal-regulatory protein alpha, SHLD1, SGK2, SFRS6, Serinethreonine kinase 35, SERINC3, SEMG2, Semenogelin I, SEC23B
Director Teppo Kröger (teppo.kroger(at) Vice director Sirpa Wrede (sirpa.wrede(at) Coordinator Emilia Leinonen (emilia.a.leinonen(at) ...
Sirpa Leppä group explores molecular mechanisms behind lymphoma pathogenesis and therapy response, and searches prognostic and predictive biomarkers.
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Biohit Oyj Stock Exchange Release June 11, 2014 at 5 p.m. local time (EEST) MEP Sirpa Pietikäinen asked the Commission, whether the Commission, in the light of research which stresses the carcinogenic nature of acetaldehyde, does intend to set a limit for acetaldehyde in food or alcoholic beverages?
The identification of Rap1 effector proteins has provided important insights into mechanisms by which Rap1 regulates T-cell receptor (TCR) signaling to integrins. A constitutively active Rap1 construct, Rap1G12V, was used as a bait in a yeast two-hybrid screen to identify RAPL as a Rap1-binding protein.[3]. Overexpression of RAPL enhances LFA-1 clustering and adhesion, and RAPL-deficient lymphocytes and dendritic cells exhibit impaired adhesion and migration.[4] RAPL is also an integrin-associated protein as RAPL polarizes to the immunological synapse following antigen stimulation of T cells, colocalizes with LFA-1 following TCR or chemokine stimulation, and co-immunoprecipitates with LFA-1 in a Rap1-dependent manner (108). This interaction between RAPL and LFA-1 is dependent on lysine residues at positions 1097 and 1099 in the juxtamembrane region of the αL-subunit cytoplasmic domain. This is a functionally significant region of the αL cytoplasmic domain as deletion of the adjacent GFFKR ...
Sirpa encodes an Ig superfamily receptor expressed on macrophages, dendritic cells, and neurons. SIRPα and its ubiquitously expressed ligand CD47 interact through their respective Ig variable region (IgV) like domains . Upon binding CD47, SIRPα immunoreceptor tyrosine- based inhibition motifs mediate inhibitory signals via recruitment of the src homology-2 domain containing protein tyrosine phosphatases SHP-1 and SHP-2 leading to decreased phagocytosis by macrophages, inhibition of neutrophil migration, and attenuated production of the inflammatory cytokine TNF
Flow cytometry and mass spectrometry are widely used analytical tools in cancer research. Flow cytometry is known for cell counting, cell sorting and cancer biomarker discovery. Mass spectrometry is unparalleled in its ability to selectively detect and quantify target analytes at the molecular level. The combination of flow cytometry to isolate specific cell subtypes from biological fluids such as blood and mass spectrometry to quantify proteins contained in the selected cells provides a new approach to studying protein expression in specific cell subtypes. We have used this combination to investigate the normal levels of CD47 and SIRPA proteins in CB8+ T-cells, CD4+ T-cells, CD14+ monocytes, CD33+ myeloid cells and CD56+ NK cells isolated from blood specimens as a first step toward better understanding of how the CD47/SIRPA protein levels in these cells are affected by cancer and cancer treatment.. Citation Format: Carmen Fernandez-Metzler, Renold Capocasale. LC-MS/MS quantification of proteins ...
A cell-cell contact between microglial SIRPα and CD47 on neighboring cells is a critical module for phase conversion of microglia in the brain white matter and controls demyelination.
PLANEGG, MUNICH and HALLE (SAALE), GERMANY / ACCESSWIRE / July 8, 2019 / MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ: MOR) and
... was first identified as a tumor antigen on human ovarian cancer in the 1980s. Since then, CD47 has been found to be ... "Entrez Gene: CD47 CD47 molecule". Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L (December 2012). "CD47 update: a ... is elevated in CD47-null endothelial cells and a human T cell line lacking CD47. Activation of CD47 with TSP-1 in wild-type ... 1994). "Rh-related antigen CD47 is the signal-transducer integrin-associated protein". J. Biol. Chem. 269 (3): 1567-70. doi: ...
2006). "Adhesion of human T cells to antigen-presenting cells through SIRPbeta2-CD47 interaction costimulates T-cell ... Brooke G, Holbrook JD, Brown MH, Barclay AN (2004). "Human lymphocytes interact directly with CD47 through a novel member of ...
Recently, the marker CD47 was found to have anti-phagocytic signals to macrophages and inhibits natural killer (NK) cells. This ... White Cell Differentiation Antigens. Oxford University Press. Knapp, W; et al. (1989). Leucocyte Typing IV. Oxford University ... "CD Antigens" (PDF). abcam. 2009. Retrieved 2014-11-22. Passlick B, Flieger D, Ziegler-Heitbrock HW (1989). "Identification and ... The CD designations were used to describe the recognized molecules, but had to be clarified by attaching the term antigen or ...
CD51+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) ITGAV Info with links in the Cell Migration ... "The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by ... "Entrez Gene: ITGAV integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51)". Hermann P, Armant M, Brown E, ...
Additionally, growing evidence supports the employment of tumor antigen-specific T cell response in response to anti-CD47 ... Dendritic cells are antigen presenting cells (APCs) in the mammalian immune system. In cancer treatment they aid cancer antigen ... Unlike CAR-T's cell surface antigens, TCR-T can recognize that larger set of intracellular antigen fragments. However, TCR-T ... Many tumor cells overexpress CD47 to escape immunosurveilance of host immune system. CD47 binds to its receptor signal- ...
SIRPA interacts with CD47, a regulator of phagocytosis. This family also interacts with surfactant protein D. The ... Zimmermann, Wolfgang; Kammerer, Robert (December 2016). "Coevolution of paired receptors in Xenopus carcinoembryonic antigen- ... and CD47: Structure, Function, and Therapeutic Target". Annual Review of Immunology. 32 (1): 25-50. doi:10.1146/annurev-immunol ... "CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence". Journal of Experimental ...
... signal CD47, and exposure of novel antigens that bind endogenous antibodies. Neutrophils have a daily rhythm of entry and exit ... Antigen recognition causes phosphatidylserine exposure on activated T-cells, which is recognized by Tim-4 on macrophages, ... "Don't-eat-me" signals include CD47, which when expressed on the surface of a cell, inhibit phagocytosis of that cell, by ... More recently it has become clear that most human cancer cells overexpress CD47 on their surface to prevent themselves being ...
The Rh antigens appear to exist as a multisubunit complex of CD47 (MIM 601028), LW (MIM 111250), glycophorin B (MIM 111740), ... The Rh blood group antigens (MIM 111700) are associated with human erythrocyte membrane proteins of approximately 30 kD, the so ... Dahl KN, Westhoff CM, Discher DE (Feb 2003). "Fractional attachment of CD47 (IAP) to the erythrocyte cytoskeleton and visual ... RhAG blood group system in the BGMUT blood group antigen gene mutation database v t e (Articles with short description, Short ...
... antigens, cd45 MeSH D23.050.301.264.035.146 - antigens, cd46 MeSH D23.050.301.264.035.147 - antigens, cd47 MeSH D23.050.301.264 ... antigens, cd45 MeSH D23. - antigens, cd46 MeSH D23. - antigens, cd47 MeSH D23. - ... antigens, cd15 MeSH D23.101.100.900.131 - antigens, cd31 MeSH D23.101.100.920 - antigens, ly MeSH D23.101.100.930 - antigens, ... forssman antigen MeSH D23.050.285.018 - antigens, cd24 MeSH D23.050.285.025 - antigens, cd30 MeSH D23.050.285.040 - antigens, ...
In Garcia's most recent work, his lab developed a peptide-MHC library technology that has enabled the discovery of antigens for ... In 2013, Garcia's group developed high affinity antagonists of the receptor CD47 that potently enhance the antitumor effects of ... They also reported a new technology using yeast-displayed peptide-MHC molecules to identify tumor antigens recognized by Tumor ... Garcia later determined that the therapeutic effects of CD47 blockade require combination therapy with checkpoint blockade ...
... but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen, but this was later ... The reason why most of the cells are not destroyed is the presence of another molecule with signal CD47, which blocks CRT. ... Hence antibodies that block CD47 might be useful as a cancer treatment. In mice models of myeloid leukemia and non-Hodgkin ... This association prepares the MHC class I for binding an antigen for presentation on the cell surface. Calreticulin is also ...
SIRPα recognizes CD47, an anti-phagocytic signal that distinguishes live cells from dying cells. CD47 has a single Ig-like ... 1997). "BIT, an immune antigen receptor-like molecule in the brain". FEBS Lett. 411 (2-3): 327-34. doi:10.1016/S0014-5793(97) ... The extracellular domain of SIRP α binds to CD47 and transmits intracellular signals through its cytoplasmic domain. CD47- ... Surfactant protein A and D are soluble ligands, highly expressed in the lungs, that bind to the same region of SIRPα as CD47 ...
January 2008). "Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals". Journal of ... April 2019). "Simultaneous blocking of CD47 and PD-L1 increases innate and adaptive cancer immune responses and cytokine ... In 1995, Robert Conry demonstrated that intramuscular injection of naked RNA encoding carcinoembryonic antigen elicited antigen ... There are a few phase I and II clinical trials using IVT mRNA encoding combinations and it shows that antigen-specific CD8+ and ...
Human leukocyte antigen-DRB1*15 haplotype is a potential risk factor of MS. Because of the increased likelihood of the mother's ... These are especially notable due to the fact that overexpression of these miRNA's cause downregulation of CD47, leading to ... The CTLA-4 gene produces an antigen of the same name that is presented on killer T-cells and allows for the suppression of the ... Methylation of this gene represses production of the antigen CTLA-4-a pattern seen in a significant majority of myasthenia ...
TAMs mediate the effects of antitumor antibodies and genetically engineered ligands that interact with CD47 to prevent the CD47 ... One such antigen was MAGE-A1. The coexistence of a progressing melanoma with melanoma-specific T cells implicitly does not ... in which clinical ACT trials with chimeric antigen receptor T cells have demonstrated efficacy. 80-90% of cancer are carcinomas ... complexes that activate intratumoral DCs to cross-present antigen to CD8+ T cells. They are targeted against oncogenic ...
A different approach to CRC is to inhibit CD47 - a membrane protein that is the thrombospondin-1 receptor. Loss of CD47 permits ... DC-like antigen-presenting cells obtained from human induced pluripotent stem cells can serve as a source for vaccination ... Thrombospondin-1 is a key environmental signal that inhibits stem cell self-renewal via CD47. Thus, CD47 antagonists enable ... CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells in vitro and in vivo. ...
"Endoscopic Molecular Imaging of Human Bladder Cancer Using a CD47 Antibody". Science Translational Medicine. 6 (260): 260. doi: ... "High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered ...
A bispecific antibody targeting GPC3 and CD47 induced enhanced antitumor efficacy against dual antigen-expressing HCC. *Kaixin ... Experiments with dual antigen-expressing HCC mouse models showed that the bispecific antibody enhances innate-immune responses ... Broad application of chimeric antigen receptor (CAR) T cell therapy is limited by T cell dysfunction, development of T cell ... Du and colleagues generated a bispecific antibody that co-engages hepatocellular carcinoma (HCC)-associated GPC3 and CD47, an ...
The in-depth report on the Leukocyte Surface Antigen CD47 market assists the buyers like business owners, marketing personnel, ... "Leukocyte Surface Antigen CD47 Market Overview:. The in-depth report on the Leukocyte Surface Antigen CD47 market assists the ... Leukocyte Surface Antigen CD47 Market to Witness Huge Growth by 2030 , Size, Trends, Applications, Types, End-User. The in- ... Regional Analysis For Leukocyte Surface Antigen CD47 Market:. North America (the United States, Canada, and Mexico). Europe ( ...
CD47, CD antigen 47; E2F1, E2 Transcription factor 1; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells ... This gives rise to the interleukin 1β isoform, which induced NF-κB transcription of the CD47 receptor. This cell surface ... This stimulates the IL-1β-induced NF-κB-mediated transcription of CD47, allowing the tumour cells to avoid phagocytosis by ... 5) (93). The study further revealed a significant association amongst SRSF10, mIL1RAP and CD47 expression in tissues of the ...
Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 microg of MWCNT or saline control via ... Evaluation of performance characteristics of hepatitis B e antigen serologic assaysExternal. Mixson-Hayden T, Purdy MA, Ganova- ... Lung and plasma NOx were reduced in the WT + MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged ... It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may ...
CD47 antigen (Rh-related antigen, integrin-associated signal transducer). CD47. NM_001025079 ...
Antigens & Antibodies. PACE Program Number. 437-903-20. Florida Course Number. 20-796132. ... Anti-CD47 y su impacto en la inmunohematología. *Spanish. *1 hour. Launch Course ...
I dont know what the role of CD47 is but. eliminating MHC I and II is not enstop regection since there are minor ... histocompatibility antigens that lead to long term rejection. My guess; CD47 overexpression downregulates the minor ... class I and II genes are inactivated and CD47 is over-expressed. These hypoimmunogenic iPSCs retain their pluripotent stem cell ...
To date, it is clear that certain anti-human CD1b, CD14, CD18, CD44, CD45, CD47, CD49c, CD61, CD68, CD91, CD95, CD163 and ... Technical Abstract: The latest human lekocyte differentiation antigen (HLDA8) workshop included an Animal Homologues section. ... mw of antigen, and, if available, reaction with cloned swine gene product. ...
CD47 ligation by TSP1 on CD8+ T cells reduces activation, antigen-mediated cytotoxicity of melanoma cells, and metabolic ... We examined Jurkat T cells with and without (CD47-) CD47 expression, WT, cd47-/- primary CD8+ T cells, and Pmel-1 WT and CD47 ( ... WT and CD47- Jurkat T cells, (D, E) naïve and activated WT and cd47-/- CD8+ T cells and (F) WT and CD47 targeted (CD47(-)) Pmel ... The CD8+ T cells derived from WT mice express CD47 while cd47-/- CD8+ T cells lack CD47 expression due to a heterogeneous ...
We find that loss of APMAP synergizes with tumour antigen-targeting monoclonal antibodies and/or CD47-blocking monoclonal ... Lymphocyte antigen 6 complex, locus E (LY6E) has been implicated in the malignant progression of various types of cancers; ... In cancer cells, beyond known factors such as CD47, we identify many regulators of susceptibility to ADCP, including the poorly ... Monoclonal antibody therapies targeting tumour antigens drive cancer cell elimination in large part by triggering macrophage ...
OSE-172 has the potential to enhance anti-tumor immunity by improving T cell activity through enhancement of DC antigen ... OSE-172 prevents the ligand CD47 from binding to and triggering the cellular inhibitory effects of SIRP-alpha. ...
Antigens, CD45. Leukocyte Common Antigens. Antigens, CD46. Membrane Cofactor Protein. Antigens, CD47. CD47 Antigen. ... Antigens, CD98 Heavy Chain. Fusion Regulatory Protein 1, Heavy Chain. Antigens, CD98 Light Chains. Fusion Regulatory Protein 1 ... Antigen Peptide Transporter-1. ATP-Binding Cassette Sub-Family B Member 2. ... Antigen Peptide Transporter-2. ATP-Binding Cassette, Sub-Family B, Member 3. ...
Antigens, CD45. Leukocyte Common Antigens. Antigens, CD46. Membrane Cofactor Protein. Antigens, CD47. CD47 Antigen. ... Antigens, CD98 Heavy Chain. Fusion Regulatory Protein 1, Heavy Chain. Antigens, CD98 Light Chains. Fusion Regulatory Protein 1 ... Antigen Peptide Transporter-1. ATP-Binding Cassette Sub-Family B Member 2. ... Antigen Peptide Transporter-2. ATP-Binding Cassette, Sub-Family B, Member 3. ...
CD47 Antigen Entry term(s). Antigen, CD47 Antigen, IAP-50 Antigens, CD47 CD47 Antigens CD47, Thrombospondin-1 Receptor IAP 50 ... Antigen, CD47. Antigen, IAP-50. Antigens, CD47. CD47 Antigens. CD47, Thrombospondin-1 Receptor. IAP 50 Antigen. IAP-50 Antigen ... 2018; see ANTIGENS, CD47 2006-2017; CD47 ANTIGEN was indexed under ANTIGENS, CD 2005; and under CARRIER PROTEINS 1993-2004. ... antígeno CD47. Entry term(s). antígeno IAP-50 antígenos CD47 proteína p50 asociada a integrinas receptor CD47 de trombospondina ...
Antigens, CD45. Leukocyte Common Antigens. Antigens, CD46. Membrane Cofactor Protein. Antigens, CD47. CD47 Antigen. ... Antigens, CD98 Heavy Chain. Fusion Regulatory Protein 1, Heavy Chain. Antigens, CD98 Light Chains. Fusion Regulatory Protein 1 ... Antigen Peptide Transporter-1. ATP-Binding Cassette Sub-Family B Member 2. ... Antigen Peptide Transporter-2. ATP-Binding Cassette, Sub-Family B, Member 3. ...
Lymphocyte antigen CD47 Active Synonym false false 1232476016 CD47 - Cluster of differentiation antigen 47 Active Synonym false ... Lymphocyte antigen CD47 (substance). Code System Preferred Concept Name. Lymphocyte antigen CD47 (substance). ...
Innovent Announces First Patient Dosed in a Phase I Clinical Trial of Anti-CD47 Monoclonal Antibody ... In vitro and in vivo experiments have shown that IBI188 can bind to the CD47 antigen on the surface of tumor cells, block the ... "CD47 is a dont eat me signal; the CD47-SIRPα mechanism is hijacked in many malignant tumors to escape immune mediated ... CD47 targets macrophages and suppresses phagocytosis by interacting and activating the inhibitory receptor SIRPα. Anti-CD47 ...
cd47 antigen (2) * femur (2) * host (organism) (2) * leukemia (2) * leukemia, myelocytic, acute (2) ... CD47-Sirpα Interaction Modulates Homing and Engraftment of Human Acute Myeloid Leukemia Stem Cells in Mice. ...
LEUKOCYTE SURFACE ANTIGEN CD47 source organism Homo sapiens pdb deposition date. 2008-04-22. ... Paired Receptor Specificity Explained by Structures of Signal Regulatory Proteins Alone and Complexed with Cd47. pubmed doi ... V-set_CD47. CD47 immunoglobulin-like domain. ABCD. PF08204 V-set_CD47. CD47 immunoglobulin-like domain. ... V-set_CD47. CD47 immunoglobulin-like domain. ABCD. PF08204 V-set_CD47. CD47 immunoglobulin-like domain. ...
oregon; chiles; Aged; CD47 Antigen; Female; Humans; Immune Checkpoint Inhibitors; Immunoglobulin G; Male; Maximum Tolerated ... Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory ... a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or ...
Summary of CD47 expression in human tissue. Cytoplasmic and membranous expression in several tissues. ... Blood group antigen proteins. Cancer-related genes. Candidate cardiovascular disease genes. CD markers. Citric acid cycle ... CD47 molecule. Protein classi. Protein class the gene product belongs to according to selected gene lists. List of protein ... Under the antigens, the maximum percent sequence identity of the protein to all other proteins from other human genes is ...
... anti-CD47 mAb, or both anti-CD24 mAb and anti-CD47 mAb, as compared to IgG control (n = 3 macrophage donors challenged with n ... Pirruccello, S. J. & LeBien, T. W. The human B cell-associated antigen CD24 is a single chain sialoglycoprotein. J. Immunol. ... CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkins lymphoma. N. Engl. J. Med. 379, 1711-1721 (2018). ... The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl Acad. ...
Cd47 CD47 antigen (Rh-related antigen, integrin-associated signal transducer). (Aliases: AA407862,B430305P08Rik,9130415E20Rik, ... Cd47 biological process predictions. Show only novel predictions. Highlight processes of functional analogs. Filter by process ... Cd47 disease predictions. Disease predictions are made from cross-annotation of human disease genes to the identified ...
CD47. CD47 antigen (Rh-related antigen, integrin-associated signal transducer). U: 2 ...
CD47 - CD molecules. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug ... CD47 antigen , CD47 antigen (Rh-related antigen, integrin-associated signal transducer) , CD47 antigen (Rh-related antigen , ... CD47 is a ubiquitously expressed membrane protein that is a marker of self. It is a ligand of SIRPα. The CD47/SIRPα anti- ... 2017) Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for ...
RECENT FINDINGS: AML blasts and leukemic stem cells express several antigens, including CD33, CD47, CD70, CD123, and CLEC12A. ... The first-in-class anti-CD47 antibody magrolimab and anti-CD70 antibody cusatuzumab in combination with hypomethylating agent ( ... This article provides an overview of immunologically relevant antigen targets expressed on the leukemic cells and synopsizes ... leukemic cell surface antigens and so forth. AREAS COVERED: This article provides an overview of the pathophysiology of AML in ...
CD47 is involved with increased cell adhesion in SCD patients as part of disease mechanism (45, 46). CD47 expressed on SCD ... Decrease of Very Late Activation Antigen-4 and CD36 on Reticulocytes in Sickle Cell Patients Treated With Hydroxyurea. Blood ( ... Mechanism of CD47-Induced α4β1 Integrin Activation and Adhesion in Sickle Reticulocytes. J Biol Chem (2004) 279:42393-402. doi ... Role of CD47 as a Marker of Self on Red Blood Cells. Science (2000) 288(5473):2051-4. doi: 10.1126/science.288.5473.2051 ...
IAP-50 Antigen use CD47 Antigen IAP1 Protein use Baculoviral IAP Repeat-Containing 3 Protein ... I-A Antigen use Histocompatibility Antigens Class II I-A-Antigen use Histocompatibility Antigens Class II ... Ia Like Antigens use Histocompatibility Antigens Class II Ia Like Antigens, Human use HLA-D Antigens ... Ia-Like Antigens use Histocompatibility Antigens Class II Ia-Like Antigens, Human use HLA-D Antigens ...
CD47: this surface protein acts as a "dont eat me!" signal that protects cancer from being consumed by certain immune cells; ... Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target ... MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but can become reactivated in ... In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti- ...
CD47 Blockade as an adjuvant immunotherapy for resectable pancreatic cancer. Michaels, A. D., Newhook, T. E., Adair, S. J., ... Antigen recognition in autoimmune diabetes: A novel pathway underlying disease initiation. Wan, X. & Unanue, E. R., Dec 1 2018 ... CD36 Mediates Cell-Surface Antigens to Promote Thymic Development of the Regulatory T Cell Receptor Repertoire and Allo- ...
  • In targeting SIRP- alpha, OSE-172 prevents the ligand CD47 from binding to and triggering the cellular inhibitory effects of SIRP-alpha. (
  • the CD47-SIRPα mechanism is hijacked in many malignant tumors to escape immune mediated clearance. (
  • CD47 targets macrophages and suppresses phagocytosis by interacting and activating the inhibitory receptor SIRPα. (
  • In vitro and in vivo experiments have shown that IBI188 can bind to the CD47 antigen on the surface of tumor cells, block the CD47-SIRPα signaling pathway, inhibit the "Don't Eat Me" signal, and promote the phagocytosis of tumor cells by macrophages, thereby exerting an anti-tumor effect. (
  • CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha ( SIRPα ). (
  • Trillium Therapeutics have two anti-SIRPα fusion proteins in Phase 1 (TTI-621 and TTI-622), and other companies have additional CD47/SIRPα-disrupting agents in preclinical testing ( e.g . (
  • The expression patterns of CD47 and its receptor, SIRPα, correlated with peak pruning in the developing retinogeniculate system, and mice lacking these proteins exhibited increased microglial engulfment of retinogeniculate inputs and reduced synapse numbers in the dorsal lateral geniculate nucleus. (
  • Taken together, these results demonstrate that CD47-SIRPα signaling prevents excess microglial phagocytosis and show that molecular brakes can be regulated by activity to protect specific inputs. (
  • CD47 is overexpressed on many cancer cells and binds SIRPα on immune phagocytic cells to produce a "don't eat me" signal. (
  • Targeting the CD47-signal-regulatory protein α (SIRPα) pathway represents a novel therapeutic approach to enhance anti-cancer immunity by promoting both innate and adaptive immune responses. (
  • Unlike CD47, which is expressed ubiquitously, SIRPα expression is mainly restricted to myeloid cells and neurons. (
  • Therefore, compared to CD47-targeted therapies, targeting SIRPα may result in differential safety and efficacy profiles, potentially enabling lower effective doses and improved pharmacokinetics and pharmacodynamics. (
  • IMM2902 inhibits tumor cell growth and proliferation by blocking HER2 and promoting HER2 degradation, CD47/SIRPα inhibitory signals to cytotoxic T cells, and destroys tumor cells by enhancing ADCP, ADCC, and potentially antibody-dependent cellular trogocytosis (ADCT). (
  • The company's lead wholly owned program, SL-172154 (SIRPα-Fc-CD40L), which is designed to block the CD47 immune checkpoint and simultaneously agonize the CD40 pathway, is being evaluated in a Phase 1 trial. (
  • Preclinical studies have shown that interrupting the CD47-SIRPα signaling pathway promotes anti-tumor activity against human cancers, both in vitro and in vivo. (
  • CD47 binds to a myeloid and neuronal cell receptor called signal regulatory protein α (SIRP α ), which initiates a signaling cascade within the bound phagocyte via immunoreceptor tyrosine-based inhibition motifs to inhibit immunoglobulin- or complement-induced favored cancer therapeutic because CD47 is widely expressed across cell types. (
  • Antibodies blocking the CD47/SIRPα signal pathway can effectively stimulate macrophage-mediated phagocytosis of tumor cells, which becomes a promising approach for tumor immunotherapy. (
  • 2018-8-28 2019-12-11 · Our research provided evidence that CD47 blockade could sensitize NSCLC to anti-angiogenic therapy and potentiate its anti-tumor effects by enhancing macrophage infiltration and tumor cell destruction, providing novel therapeutics for NSCLC by disrupting CD47/SIRPα interaction and angiogenetic axis. (
  • 2020-4-2 · CD47 is an immune checkpoint protein that downregulates both the innate and adaptive anti-tumor immune response via its counter receptor SIRPα. (
  • Biologics, including humanized CD47 monoclonal antibodies and decoy SIRPα receptors, that block the SIRPα-CD47 interaction, are currently being developed as cancer immunotherapy agents. (
  • SUZHOU, China I January 14, 2019 I Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, announced today that the first patient has been successfully dosed in a phase I clinical trial of anti-CD47 monoclonal antibody (IBI188) for patients with advanced malignancies. (
  • Anti-CD47 mono therapy and combination therapy has shown promising efficacy in several types of solid tumor and in refractory/relapsed non-Hodgkin Lymphoma. (
  • Fc-mediated opsonization also depletes RBCs, raising concerns that potential on-target anemia could result from the use of anti-CD47 agents. (
  • Instead, this CD47 loss requires anti-CD47 cross-linking between RBCs and non-RBCs. (
  • which sensitizes mice to anti-CD47 immu- notherapy in a STING-and IFN-dependent fashion. (
  • However, adverse side effects and limited … Therapeutics, Targets, and Chemical Biology Therapeutic Antibody Targeting of CD47 Eliminates CD47 could eliminate primary human ALL in vitro and in vivo, to determine the preclinical feasibility of an anti-CD47 anti-body therapy in standard and high-risk ALL. (
  • The in-depth report on the Leukocyte Surface Antigen CD47 market assists the buyers like business owners, marketing personnel, stake holders, and more to boost their sale and ultimately impact the industry growth for the forecast period 2022 - 2030. (
  • This report helps to streamline your business by accessing the level of competition and ensuring sterilization in the Leukocyte Surface Antigen CD47 market. (
  • The study gives a comprehensive view of the Leukocyte Surface Antigen CD47 market, both today and in the future. (
  • What will you get in the Leukocyte Surface Antigen CD47 Market report? (
  • Detail study of Leukocyte Surface Antigen CD47 market size, growth margin, revenue share, growth opportunities, new launches and upcoming challenges. (
  • Quantitative and qualitative analysis of Leukocyte Surface Antigen CD47 market by types, applications, region and end-user. (
  • 1 day ago · Apr 15, 2021 (Heraldkeepers) -- The Leukocyte Surface Antigen CD47 market report provides a detailed analysis of global market size, regional and 2020-12-7 · CD47 is a protective "don't eat me" signal that blocks the ability of certain immune cells to destroy the tumor. (
  • People in the experimental group will receive IV cyclophosphamide and fludarabine for 3 days followed by a single infusion of the cell therapy, which involves patients' own T-cells being engineered to express receptors keyed to their tumor antigen-mutation profiles. (
  • Moreover, PTPN2 deletion in T cells expressing a chimeric antigen receptor (CAR) specific for the oncoprotein HER-2 increased the activation of the Src family kinase LCK and cytokine-induced STAT-5 signalling, thereby enhancing both CAR-T cell activation and homing to CXCL9/10 expressing tumours to eradicate HER-2+ mammary tumours in vivo. (
  • In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. (
  • HLH has two forms: primary (familial autosomal recessive) or secondary (related to infections, malignancy, autoimmune and metabolic disorders, transplantations, chimeric antigen receptor T-cell therapies, etc.) form. (
  • We find that loss of APMAP synergizes with tumour antigen-targeting monoclonal antibodies and/or CD47-blocking monoclonal antibodies to drive markedly increased phagocytosis across a wide range of cancer cell types, including those that are otherwise resistant to ADCP. (
  • Preclinical modeling studies were conducted with intact and Fc-deficient anti-mouse CD47 (MIAP410) and anti-human CD47 (magrolimab) antibodies in murine models, including C57BL/6J B-hSIRPA/hCD47 mice. (
  • The development of a suitable immunoassay depends on the availability of the protein antigen and the generation of an immune response in the host animal and the subsequent production of antibodies. (
  • Owing to the inherent diversity of an immune response and the structure and binding affinity of different antibodies for the same antigen, antibodies used in one assay or platform behave differently from those used in another, unless they are the same clone of monoclonal antibody. (
  • Polyclonal antibodies have the advantage of being able to recognize multiple epitopes of a complex antigen, but inconsistency in production has hindered their use. (
  • Monoclonal antibody therapies targeting tumour antigens drive cancer cell elimination in large part by triggering macrophage phagocytosis of cancer cells1-7. (
  • IBI188 is a fully human monoclonal antibody targeting CD47. (
  • Background CD47 is an integral membrane protein that alters adaptive immunosurveillance when bound to the matricellular glycoprotein thrombospondin-1 (TSP1). (
  • In cancer cells, beyond known factors such as CD47, we identify many regulators of susceptibility to ADCP, including the poorly characterized enzyme adipocyte plasma membrane-associated protein (APMAP). (
  • Their simple genetic structure allows easy re-engineering of the protein to introduce new antigen-binding characteristics or attach labels. (
  • This trial involves the enhancement of current immune checkpoint-based immunotherapy with ALX148, an agent that inhibits CD47 (a trans-membrane protein that is highly expressed on the surface of many solid tumors as compared to normal cells). (
  • CD47 is a protein that up-regulated in many cancers as a way to escape immune surveillance. (
  • 2020-1-13 · CD47, the integrin-related protein, plays an important role in immune resistance and escape of tumor cells. (
  • Antigens, CD18" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • This graph shows the total number of publications written about "Antigens, CD18" by people in UAMS Profiles by year, and whether "Antigens, CD18" was a major or minor topic of these publications. (
  • Below are the most recent publications written about "Antigens, CD18" by people in Profiles over the past ten years. (
  • This program aims to develop CD47 × CD19 therapeutic bispecific antibody for immuno-oncology. (
  • Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD47 1 , programmed cell death ligand 1 (PD-L1) 2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M) 3 . (
  • Door hun stabiel en oplosbaar karakter, hoge affiniteit en specificiteit voor hun ligand en uitstekende weefsel penetratie zijn nanobodies bijzonder geschikt om in ons geval tumoren te targeten. (
  • Mijn scriptie « Nanobody-mediated imaging and inhibition of the immune checkpoint ligand PD-L1 » leert dat het gebruik van nanobodies, gericht tegen het inhibitorisch signaal PD-L1, veelbelovend is voor de diagnose en behandeling van kankerpatiënten. (
  • The latest human lekocyte differentiation antigen (HLDA8) workshop included an Animal Homologues section. (
  • CD47 expression is hijacked by cancer cells to evade immune surveillance and macrophage-mediated removal. (
  • Context: Magrolimab is an antibody blocking CD47, a "don't eat me" signal expressed on cancer cells, to escape immune surveillance and macrophage-mediated clearance. (
  • Tumor antigen-specific cytotoxic T cells are present in advanced cancers but often fail to induce tumor rejection (1-3) because cancer cells utilize many tumor-intrinsic mechanisms to escape immune- mediated destruction. (
  • This has galvanized the leukemic research community leading to the discovery and development of agents that specifically target gene mutations, molecularly agnostic therapies that exploit immune environment, apoptotic pathways, leukemic cell surface antigens and so forth. (
  • Studies on liver CSCs have uncovered various cell surface antigens such as EpCAM, CD90, CD47, CD13, CD24, and CD133 that identify subpopulations of tumor-initiating cells in HCC ( 3 - 8 ). (
  • OSE-172 has the potential to enhance anti-tumor immunity by improving T cell activity through enhancement of DC antigen presentation functionality, potentiating the phagocytic and inflammatory properties of macrophages in the tumor microenvironment and enabling differentiation of MDSCs to an effector state. (
  • Don't Eat Me" CD47 signal allows healthy cells to escape the phagocytosis by macrophages and other innate immune cells. (
  • Forty Seven is a clinical-stage immuno-oncology company focused on developing novel checkpoint therapies to activate macrophages in the CD47 is highly expressed on myeloma cells and a potential therapeutic candidate for myeloma therapies. (
  • The NCI seeks partners interested in in-licensing or co-development collaboration on CD47-targeting therapeutics for cardioprotection and autophagy modulation. (
  • Trillium Therapeutics is a leader in the CD47 inhibitor space in terms of data claims, and Pfizer has recently taken an interest. (
  • On July 15, 2022, ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (hereinafter referred to as "ImmuneOnco" and the company) announced that the first global CD47×HER2 bispecific molecule (IMM2902) have received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA) for breast cancer. (
  • IMM2902 is a bi-specific molecule for targets CD47 and HER2 developed based on our own R&D platform. (
  • IMM2902, as one of our main products, is currently the only CD47×HER2 bispecific molecule that has entered clinical stage in the world. (
  • Here we show that both mouse and human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed. (
  • DSP107 targets CD47-overexpressing tumors, simultaneously blocking macrophage inhibitory signals and delivering an immune costimulatory signal to tumor antigen-specific, activated T-cells. (
  • At the same time, it doesn't bind to human erythrocytes so as avoiding the 'antigen sink effect' thus greatly enhancing the specific synergistic effect of two targets against tumors. (
  • The present disclosure relates to agents that bind CD47 and comprise an Fc domain, and methods of identifying patients likely to respond to said agents. (
  • CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. (
  • Methods A syngeneic B16 mouse melanoma model was performed to determine if targeting CD47 as monotherapy or in combination with anti-PD-1 impacted tumor burden. (
  • Targeting CD47 allowed CD8+ T cells to overcome this TSP1 interaction to sustain these functions. (
  • however, targeting CD47 restored glycolysis when CD8+ T cells were exposed to TSP1, suggesting CD47 mediated metabolic reprogramming of T cells. (
  • Targeting CD47 in combination with anti-PD-1 treatment further decreased tumor burden compared with monotherapy and control. (
  • Conclusion CD47/TSP1 expression could serve as a marker to predict patient response to immune checkpoint blockade treatment, and targeting this pathway may preserve T cell activation, proliferation, effector function, and bioenergetics to reduce tumor burden as a monotherapy or in combination with anti-PD-1. (
  • Intralesional TTI-621, a novel biologic targeting the innate immune checkpoint CD47, in patients with relapsed or refractory mycosis fungoides or Sézary syndrome: a multicentre, phase 1 study. (
  • Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) proteins transformed the management of advanced cancers. (
  • Preclinical studies found that CD47 is critical to RBC homeostasis, with CD47 deficiency decreasing RBC half-life. (
  • Our preclinical studies with mouse models revealed that CD47 removal is mechanistically independent of previously described RBC antigen modulation mechanisms and cellular compartments. (
  • CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin's lymphoma. (
  • Results Human malignant melanoma tissue had increased CD47 and TSP1 expression within the tumor microenvironment compared with benign tissue. (
  • Cell lysis results in the release of viral progeny, pathogen-associated molecular patterns (PAMP), damage-associated molecular patterns (DAMP), and tumor-associated antigens (TAA) into the tumor microenvironment (TME). (
  • Interaction between CD47 and SIRPa leads to activation of tyrosine phosphatases that inhibit myosin accumulation at the C4T is as differentiated as differentiated gets. (
  • Single-cell RNA-sequencing, ELISA, and flow cytometry was performed on peripheral blood mononuclear cells and plasma of melanoma patients receiving anti-PD-1 therapy to examine CD47/TSP1 expression. (
  • Additionally, non-responding patients to anti-PD-1 therapy had increased T cells expressing CD47 and circulating levels of TSP1 compared with responding patients. (
  • Since CD47/TSP1 signaling axis negatively impacts CD8+ T cells and non-responding patients to anti-PD-1 therapy have increased CD47/TSP1 expression, we targeted CD47 in combination with anti-PD-1 in a melanoma model. (
  • Additionally, the company is advancing a proprietary Gamma Delta T Cell Engager, GADLEN™, platform, which is designed to bridge gamma delta T cells to tumor antigens for the treatment of patients with cancer. (
  • Thus, blocking CD47 has emerged as a promising therapeutic strategy with early clinical data demonstrating benefit to cancer patients. (
  • Een kameel afgeleide antigen-bindend fragment, vernoemd als een nanobody, heeft de voorbije jaren veel aandacht aangetrokken bij onderzoekers uit veel domeinen. (
  • 80 of the mAb proved to be + on pig cells and are now being analyzed in more depth by confirming appropriate tissue and cell subset expression, effect of activation on expression, mw of antigen, and, if available, reaction with cloned swine gene product. (
  • A) Design from ABO and you will H antigens on the person purple tissue. (
  • CD47-deficient mice also displayed increased functional pruning, as measured by electrophysiology. (
  • In addition, CD47 was found to be required for neuronal activity-mediated changes in engulfment, as microglia in CD47 knockout mice failed to display preferential engulfment of less active inputs. (
  • Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice. (
  • Interestingly, tetramer staining showed that the precursor frequency of naive CD8 + T cells in B6 mice was about 10-fold lower than the precursor frequency for the strong OVA SIINFEKL antigen. (
  • Although circulating CB-specific T cells increased in number in all treated mice at 2 weeks post-treatment, they became undetectable in monotherapy-treated long-term survivors after tumor clearance, suggesting that antigen presentation was required for persistence. (
  • A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. (
  • This is a first-in-class agent that interferes with the recognition of CD47 on the surface of tumor cells ― the "don't eat me" signal by which cancer cells evade immune destruction. (
  • CBCs were measured, and blood and BM samples were analyzed by flow cytometry for CD47 expression on RBCs and white blood cells (WBCs). (
  • The expression off ABH antigens in frameworks and the body fluids most other than simply blood muscle was managed because of the secretor gene (FUT2), and therefore encodes an alpha step 1,2-fucosyltransferase capable of animated L-fucose so you're able to carbon 2 away from galactose (beta, 1-3) N-acetyl D-glucosamine-which has glycans. (