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 ...
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.. ...
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. ...
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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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
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 ... In the example of CD4 & CD8, these molecules are critical in antigen recognition. Others (e.g., CD135) act as cell surface ...
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 ... Many tumor cells overexpress CD47 to escape immunosurveilance of host immune system. CD47 binds to its receptor signal ... Antigens can be added to the antibody and can induce the dendritic cells to mature and provide immunity to the tumor. Dendritic ...
... 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 ... blood-group antigen expression". The Biochemical Journal. 287. 287 (1): 223-8. doi:10.1042/bj2870223. PMC 1133147. PMID 1417776 ...
... 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, ...
... 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. PMID ...
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 ...
This antigen along with other blood group antigens was used to identify the Basque people as a genetically separate group.[49] ... Because the Duffy antigen is uncommon in those of Black African descent, the presence of this antigen has been used to detect ... The Fy4 antigen, originally described on Fy (a-b-) RBCs, is now thought to be a distinct, unrelated antigen and is no longer ... The Duffy antigen is expressed in greater quantities on reticulocytes than on mature erythrocytes.[21] While the Duffy antigen ...
... 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 ...
A razón pola cal a maioría das células cancerosas non son destruídas é a presenza doutra molécula, o CD47, que bloquea a ... "A human Ro/SS-A autoantigen is the homologue of calreticulin and is highly homologous with onchocercal RAL-1 antigen and an ... Por tanto, os anticorpos que bloquean o CD47 poderían ser útiles para o tratameno do cancro. En modelos de rato de leucemnia ... "Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47". Sci Transl Med 2 ...
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 ...
Tissue Antigens (англ.)русск. : journal. - 2007. - Vol. 68, no. 6. - P. 509-517. - DOI:10.1111/j.1399-0039.2006.00726.x. - PMID ...
CD97 antigen je protein koji je kod ljudi kodiran CD97 genom.[1][2][3] ... CD47 • CD48 • CD49 (a, b, c, d, e, f) • CD50 ... and chromosomal mapping of the leukocyte activation antigen ... 2001). „Tissue distribution of the human CD97 EGF-TM7 receptor". Tissue Antigens. 57 (4): 325-31. PMID 11380941. doi:10.1034/j. ...
1997). "The Oka blood group antigen is a marker for the M6 leukocyte activation antigen, the human homolog of OX-47 antigen, ... 1992). "Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse ... Kasinrerk W, Fiebiger E, Stefanová I, Baumruker T, Knapp W, Stockinger H (1992). "Human leukocyte activation antigen M6, a ... Ok blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH ...
CD74 (англ. HLA class II histocompatibility antigen gamma chain; HLA-DR antigens-associated invariant chain) - мембранный белок ... II histocompatibility antigen gamma chaingamma chain of class II antigensIiHLA-DR antigens-associated invariant chainIa antigen ... Riberdy J.M., Newcomb J.R., Surman M.J., Barbosa J.A., Cresswell P. HLA-DR molecules from an antigen-processing mutant cell ... Machamer C.E., Cresswell P. Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens (англ.) // ...
Seligman P. A., Butler C. D., Massey E. J., etal. The p97 antigen is mapped to the q24-qter region of chromosome 3; the same ... Le Beau M. M., Diaz M. O., Plowman G. D., etal. Chromosomal sublocalization of the human p97 melanoma antigen. (англ.) // Hum. ... Plowman G. D., Brown J. P., Enns C. A., etal. Assignment of the gene for human melanoma-associated antigen p97 to chromosome 3 ... Rose T. M., Plowman G. D., Teplow D. B., etal. Primary structure of the human melanoma-associated antigen p97 ( ...
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. ...
In humans, the CD44 antigen is encoded by the CD44 gene on Chromosome 11.[5] CD44 has been referred to as HCAM (homing cell ... The CD44 antigen is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. ... Indian blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH ... "Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in ...
1991). „Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow". Blood. 78 (1): 30-7. PMID ... CD47 • CD48 • CD49 (a, b, c, d, e, f) • CD50 ... transduction-associated and cell activation-linked antigens ...
... is a co-receptor of the T cell receptor (TCR) and assists the latter in communicating with antigen-presenting cells. The ... Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies: specification, classification, ... T cells displaying CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and ... CD1+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) ...
In addition to aiding with cytotoxic T cell antigen interactions the CD8 co-receptor also plays a role in T cell signaling. The ... the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell antigen interactions. ... This affinity keeps the T cell receptor of the cytotoxic T cell and the target cell bound closely together during antigen- ... Once the T cell receptor binds its specific antigen Lck phosphorylates the cytoplasmic CD3 and ζ-chains of the TCR complex ...
1996). "CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and react with a desmosomal antigen in human ... CD47 • CD48 • CD49 (a, b, c, d, e, f) • CD50 ...
van Rhenen A., van Dongen G. A., Kelder A., et al. The novel AML stem cell associated antigen CLL-1 aids in discrimination ...
... uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate (англ.) // Blood (англ ...
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) also known as CD66e (Cluster of Differentiation 66e), is a ... 2001). "Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells". J. Biol. Chem. 276 ( ... CEACAM5, CD66e, CEA, carcinoembryonic antigen related cell adhesion molecule 5. External IDs. HomoloGene: 128801 GeneCards: ... Oikawa S, Nakazato H, Kosaki G (1987). "Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence". ...
A new ligand for human leukocyte antigen class II antigens". The Journal of Experimental Medicine. 176 (2): 327-37. doi:10.1084 ... A new ligand for human leukocyte antigen class II antigens". The Journal of Experimental Medicine. 176 (2): 327-37. doi:10.1084 ... antigen processing and presentation of exogenous peptide antigen via MHC class II. ... antigen binding. • transmembrane signaling receptor activity. • MHC class II protein binding. Cellular component. • membrane. • ...
2000). "Characterization of a new member of the TNF family expressed on antigen presenting cells.". Biol. Chem. 380 (12): 1443- ... CD47 • CD48 • CD49 (a, b, c, d, e, f) • CD50 ... independent compartments among naïve and antigen-experienced B ...
I. Partial characterization of soluble Ki-1 antigen and detection of the antigen in cell culture supernatants and in serum by ... Josimovic-Alasevic O, Dürkop H, Schwarting R, Backé E, Stein H, Diamantstein T (Jan 1989). "Ki-1 (CD30) antigen is released by ... CD30+Antigens at the US National Library of Medicine Medical Subject Headings (MeSH) ... results from cDNA cloning and sequence comparison of the CD30 antigen from different sources". Molecular Immunology. 31 (17): ...
Macrophage-1 antigen (CD11b+CD18). *VLA-4 (CD49d+CD29). *Glycoprotein IIb/IIIa (ITGA2B+ITGB3) ...
The protein also carries the Jr(a) antigen, which defines the Junior blood group system.[9] ...
"Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin". Molecular and ...
Ebert LM, McColl SR (2002). "Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes ... This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may ... dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens". J. Immunol. 167 (11): ...
It is also called Lewis x and SSEA-1 (stage-specific embryonic antigen 1) and represents a marker for murine pluripotent stem ... CD15 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH) ... CD15 (3-fucosyl-N-acetyl-lactosamine) is a cluster of differentiation antigen - an immunologically significant molecule. CD15 ...
... antigen je protein koji je kod ljudi kodiran CD97 genom.[1][2][3] ... CD47 • CD48 • CD49 (a, b, c, d, e, f) • CD50 ... and chromosomal mapping of the leukocyte activation antigen ... 2001). "Tissue distribution of the human CD97 EGF-TM7 receptor". Tissue Antigens 57 (4): 325-31. PMID 11380941. doi:10.1034/j. ...
"Entrez Gene: ITGB3 integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)".. *^ May, K. E.; Villar, J.; Kirtley, S.; ... CD61+Antigens at the US National Library of Medicine Medical Subject Headings (MeSH) ...
"Direct association of adenosine deaminase with a T cell activation antigen, CD26". Science. 261 (5120): 466-9. doi:10.1126/ ...
B cells can present antigens to a specialized group of helper T cells called TFH cells. If an activated TFH cell recognizes the ... Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help". Journal of Immunology. 149 (12): ... It binds to CD40 (protein) on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In ... Grewal, IS; Xu, J; Flavell, RA (7 December 1995). "Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand". ...
antigen processing and presentation of peptide antigen via MHC class I. • antigen processing and presentation of exogenous ... antigen processing and presentation of exogenous peptide antigen via MHC class I. • lipoprotein transport. • negative ... peptide antigen via MHC class I, TAP-dependent. • platelet degranulation. • MyD88-dependent toll-like receptor signaling ...
Primarily, the VCAM-1 protein is an endothelial ligand for VLA-4 (Very Late Antigen-4 or integrin α4β1) of the β1 subfamily of ...
Grave's disease and Hashimoto's thyroiditis are greatly increased in patients with CD.[47] Grave's disease is an autoimmune ... Al-Toma A, Goerres MS, Meijer JW, Peña AS, Crusius JB, Mulder CJ (2006). "Human leukocyte antigen-DQ2 homozygosity and the ...
antigen binding. • virus receptor activity. • protein binding. • transmembrane signaling receptor activity. • identical protein ...
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell. • T cell antigen ... CD47 · CD48 · CD49 (a, b, c, d, e, f) · CD50 ...
CD47" by people in Harvard Catalyst Profiles by year, and whether "Antigens, CD47" was a major or minor topic of these ... "Antigens, CD47" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical Subject ... Below are the most recent publications written about "Antigens, CD47" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Antigens, CD47". ...
sp,Q08722,CD47_HUMAN Leukocyte surface antigen CD47 OS=Homo sapiens OX=9606 GN=CD47 PE=1 SV=1 ... IPR006704, CD47. IPR013147, CD47_TM. IPR013270, CD47_Vset. IPR007110, Ig-like_dom. IPR036179, Ig-like_dom_sf. IPR013783, ... IPR006704, CD47. IPR013147, CD47_TM. IPR013270, CD47_Vset. IPR007110, Ig-like_dom. IPR036179, Ig-like_dom_sf. IPR013783, ... Leukocyte surface antigen CD47Add BLAST. 305. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical ...
Home , A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells ... 2015) A bispecific antibody targeting CD47 and CD20 selectively binds and eliminates dual antigen expressing lymphoma cells. ...
Global and United States Leukocyte Surface Antigen CD47 Market Research by Company, Type & Application 2013-2025 is a market ... Global Leukocyte Surface Antigen CD47 Sales Market Report 2017. Global Leukocyte Surface Antigen CD47 Sales Market Report 2018 ... Global Leukocyte Surface Antigen CD47 Market Insights, Forecast to 2025. Global Leukocyte Surface Antigen CD47 Market Status ... Figure Global Leukocyte Surface Antigen CD47 Market Size and CAGR 2013-2017 (Volume). Figure Global Leukocyte Surface Antigen ...
Canine Leukocyte surface antigen CD47,CD47 ELISA kit \ CC003 for more molecular products just contact us ... Canine Leukocyte surface antigen CD47,CD47 ELISA kit. Related products : Canine Leukocyte surface antigen CD47,CD47 ELISA kit ... Canine Leukocyte surface antigen CD47,CD47 ELISA kit / Product Detail : CC003 Canine Leukocyte surface antigen CD47,CD47 ELISA ... Canine Leukocyte surface antigen CD47,CD47 ELISA kit antibody storage GENTAUR recommends for long therm storage to freeze at - ...
ACROBiosystems provides a unique set of CD47-relevant products, including mutilple avi tag pre-biotinylated proteins, for rapid ... Immobilized Anti-CD47 MAb, Human IgG4 at 2 μg/mL (100 μL/well) can bind Biotinylated Human CD47, His,Avitag (Cat. No. CD7-H82E9 ... Anti-Human CD47 MAb (Human IgG4) captured on CM5 chip via Anti-Human IgG Fc antibodies surface, can bind Human CD47, His Tag ( ... CD47 protects the host cells by suppressing phagocytosis. Its well established that cancer cell-expressed CD47 interacts with ...
There is nothing innovative as to what we carry out at Industry Global News. We are just a typical news platform that looks after readers requirements. So, what makes us stand out as compared to others? The answer is easy. At Industry Global News, we cover a range of subjects varying from Business and Medical section to Science and Technology section, thereby wrapping a huge chunk of affairs all over the world. This is one of the main factors that make us show up in the crowd of other platforms present these days.. ...
... outlays comprehensive information on the Leukocyte Surface Antigen CD47 (Antigenic Surface Determinant Protein OA3 or Integrin ... Associated Protein or Protein MER6 or CD47) targeted therapeutics, complete with analysis by indications, stage of development ... Leukocyte Surface Antigen CD47 - Pipeline Review, H2 2017, outlays comprehensive information on the Leukocyte Surface Antigen ... Research delivers insight into the leukocyte surface antigen cd47 pipeline report Details WhaTech Channel: Industrial Market ...
Leukocyte Surface Antigen CD47 Market Size by Types, Applications, Major Regions and Major Manufacturers including the capacity ... 6.3 Leukocyte Surface Antigen CD47 Price by Type. 7 Leukocyte Surface Antigen CD47 Segment Market Analysis (by Application). ... Leukocyte Surface Antigen CD47 Market Analysis. The global Leukocyte Surface Antigen CD47 market was valued at million US$ in ... 5.1 Leukocyte Surface Antigen CD47 Production by Regions. 5.1.1 Global Leukocyte Surface Antigen CD47 Production by Regions. ...
Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also ... T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T ... pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In ... and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as ...
Shop a large selection of products and learn more about CD47, Mouse anti-Human, Clone: B6H12, BV711, BD 100 Tests; BV711 100 ... Antigen. CD47. Format. Affinity Purified. Immunogen. Purified human placental RGD-binding proteins. ...
Mouse anti-CD47, Clone: IAP/964 + B6H12.2, Novus Biologicals 0.02mg; Unlabeled Life Sciences:Antibodies:Primary Antibodies:Flow ... CD47 antigen, CD47 antigen (Rh-related antigen, integrin-associated signal transducer), CD47 glycoprotein, CD47 molecule, ... leukocyte surface antigen CD47, MER6integrin-associated signal transducer, OA3, Protein MER6, Rh-related antigen. ... CD47 Monoclonal antibody specifically detects CD47 in Human, Mouse samples. It is validated for Flow Cytometry, ...
PfMSA180 is a novel Plasmodium falciparum vaccine antigen that interacts with human erythrocyte integrin associated protein ( ... CD47) *Hikaru Nagaoka. *, Chisa Sasaoka. *, Takaaki Yuguchi. *, Bernard N. Kanoi. *, Daisuke Ito ...
Antibodies targeting the T-cell immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA4) enhance the effectiveness of ... CD47 m) alone or combined with anti-CTLA4 enhanced antigen-dependent killing of irradiated melanoma cells. Correspondingly, the ... Nath P, Pal-Nath, D, Mandal, A, Cam, MC, Schwartz AL, Roberts DD (2019) CD47 in the tumor microenvironment and CD47 antibody ... CD47 m alone or in combination with anti-CTLA4 increased CD3+ T-cell infiltration in irradiated tumors. Anti-CTLA4 also ...
Antigens, CD / physiology * CD47 Antigen * Carrier Proteins / physiology * Cell Adhesion * Cell Adhesion Molecules / physiology ...
Active Recombinant human CD47 protein (Active) is a HEK 293 Protein fragment 19 to 139 aa range, , 95% purity, , 1.000 Eu/µg ... CD47 antigen. *CD47 antigen (Rh-related antigen, integrin-associated signal transducer). *CD47 glycoprotein ... Anti-Human CD47 MAb (Human IgG4) captured on CM5 chip via Anti-Human IgG Fc antibodies surface can bind Human CD47 (His Tag) ... Anti-Human CD47 MAb (Human IgG4) captured on CM5 chip via Anti-Human IgG Fc antibodies surface, binds ab174029. ...
Buy our Recombinant Human CD47 protein. Ab126004 is a protein fragment produced in Escherichia coli and has been validated in ... CD47 antigen. *CD47 antigen (Rh-related antigen, integrin-associated signal transducer). *CD47 glycoprotein ...
CD47 blockade enhances antigen-dependent T-cell killing of irradiated 15-12RM fibrosarcoma cells. To determine whether CD47 ... S5). The ratio was highest with combined IR and CD47 morpholino or in a CD47-null microenvironment, indicating that CD47 ... CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8+ CTL-mediated tumor cell ... CD47 blockade enhances antigen-dependent T-cell killing of 15-12RM fibrosarcoma when combined with irradiation. A, 15-12RM ...
Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. ... Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. ... CD47 was first identified as a tumor antigen on human ovarian cancer in the 1980s (2). Since then, CD47 has been shown to be ... B) With CD47 blockade (with an anti-CD47 antibody), cancer cells are phagocytosed due to CD47 blockade and resulting unmasking ...
We now have examined the possible role of anti-CD47-enabled phagocytosis in antigen presentation of tumor peptides to T cells ... S1). Anti-CD47 B6H12 (blocking) mAb blocks the interaction between CD47 and SIRP-α, whereas anti-CD47 2D3 (non-blocking) ... In this system macrophages are the primary APCs that phagocytose cancer in response to anti-CD47 antibody and present antigen ... Using the ovalbumin model antigen system, anti-CD47 antibody-mediated phagocytosis of cancer cells by macrophages resulted in ...
Leukocyte Surface Antigen CD47 - Pipeline Review, H2 2019 3070 3500 2730 156 pages • By Global Markets Direct • Dec 2019 ...
CD47 Antigen / analysis * CD47 Antigen / metabolism * Coculture Techniques * Dendritic Cells / drug effects ... This inhibition of maturation depends on the expression of CD47 on erythrocytes and of its ligand SIRPalpha on DC. While ...
The dark histogram, the isotype control; the overlaying open histogram, surface expression of individual antigens. The ... CD47 Ligation Induces Apoptosis in Breast Cancer Cell Lines.. Incubation of CD47+/+ breast cancer cells with CD47 agonist ... We have reported that certain monoclonal antibodies (mAbs) versus CD47, as well as the natural CD47 ligand TSP1, and a CD47 ... CD47-Dependent Killing of Breast Cancer Cells Is Mediated via Gi.. We have reported that the effects of CD47 related to ...
Normal cells expressing CD47 create an "antigen sink" that may sequester CD47 targeting agents, preventing these agents from ... A, schematic of experimental design to detect simultaneous binding to CD20 and CD47. Biotinylated CD47 antigen was linked to a ... 4). RBCs represent a large antigen sink and potential source of toxicity with CD47 targeting agents as CD47 expression ... RBCs highly express CD47 and are a likely "antigen sink" as they are abundant and accessible to antibody in the bloodstream (22 ...
CD47 antigen (CD47) (1:200; BD Biosciences), FABP7 (1:100; kindly provided by T. Mueller, C. Birchmeier, MDC, Berlin, Germany ... c, d, g, h, PTPNS1 and CD47 signals are shown in green. a, b, e, f, PTPNS1 and CD47 signals are shown in red. Note the band- ... CD47 and GFAP (f), PTPNS1 and PSA-NCAM (c) as well as CD47 and PSA-NCAM (h). Scale bars: a, e, 100 μm; b-d, f, h, 50 μm. ... or GFAP and CD47 (b) are marked by arrows. c, d, Arrows depict examples of cells positive for PTPNS1 and HUC/D (c) or CD47 and ...
Integrin-associated protein; Integrin-associated signal transducer; Ovarian cancer antigen OA3; Rh-related antigen CD47 was ... first identified in 1987 as an antigen that is missing in red blood... ... CD47, Fig. 3 CD47 regulation of superoxide (O2−) production. TSP1 signaling through CD47 (Csanyi et al. 2012), and potentially ... CD47, Fig. 5 CD47 regulation of T cell signaling. TSP1 regulates T cell signaling via the receptors α4β1 integrin and CD47. The ...
Cd47 CD47 antigen (Rh-related antigen, integrin-associated signal transducer) MGI:96617 ...
CD47 antigen (Rh-related antigen, integrin-associated signal transducer). CD47. 37890_at. 1.9. ... CD86 antigen (CD28 antigen ligand 2, B7-2 antigen). CD86. 36270_at. −3.4. ... CD80 antigen (CD28 antigen ligand 1, B7-1 antigen). CD80. 35015_at. 4.7. ... CD209 antigen-like. CD209L. 39270_at. nc. CD36 antigen (collagen type I receptor, thrombospondin receptor). CD36. 36656_at. nc ...
Leukocyte Surface Antigen CD47 - Pipeline Review, H2 2019; Leukocyte Surface Antigen CD47 ... ... Leukocyte Surface Antigen CD47 - Pipeline Review, H2 2019SummaryAccording to the recently published report ... The report reviews latest news and deals related to Tumor Necrosis Factor Receptor Superfamily Member 4 (ACT35 Antigen or TAX ... It also reviews key players involved in Tumor Necrosis Factor Receptor Superfamily Member 4 (ACT35 Antigen or TAX ...
Targeting CD47 as a novel immunotherapy for multiple myeloma* Jennifer Sun, Washington University in St. Louis, St. Louis, ... Human chimeric antigen receptor (CAR) macrophages for cancer immunotherapy^*. Michael Klichinsky, University of Pennsylvania, ...
  • In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. (
  • CD47 plays a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. (
  • To further improve response rates, we explored combining anti-CTLA4 blockade with antisense suppression of CD47, an inhibitory receptor on T cells that limit T-cell receptor signaling and killing of irradiated target cells. (
  • CD47 is a widely expressed counter-receptor for the inhibitory phagocyte receptor SIRPα. (
  • However, CD47 also functions as a signaling receptor that determines cell fate through the regulation of several death/survival pathways, mainly through its interactions with the matricellular protein thrombospondin-1 (TSP1). (
  • Inhibition of phagocytosis occurs by CD47 binding to its cognate receptor Signal Regulatory Protein Alpha (SIRPα) on macrophages leading to tyrosine phosphatase activation and inhibition of myosin accumulation at the phagocytic synapse site, thereby preventing phagocytosis ( 1 ). (
  • The TSP receptor CD47 (integrin-associated protein) has recently been reported to mediate a novel form of apoptosis. (
  • Tumor Necrosis Factor Receptor Superfamily Member 4 (ACT35 Antigen or TAX Transcriptionally Activated Glycoprotein 1 Receptor or OX40L Receptor or CD134 or TNFRSF4) - Tumor Necrosis Factor Receptor Superfamily Member 4 or OX40 is a member of the TNF-receptor superfamily. (
  • Tumor Necrosis Factor Receptor Superfamily Member 4 (ACT35 Antigen or TAX Transcriptionally Activated Glycoprotein 1 Receptor or OX40L Receptor or CD134 or TNFRSF4) pipeline Target constitutes close to 26 molecules. (
  • The latest report Tumor Necrosis Factor Receptor Superfamily Member 4 - Pipeline Review, H2 2019, outlays comprehensive information on the Tumor Necrosis Factor Receptor Superfamily Member 4 (ACT35 Antigen or TAX Transcriptionally Activated Glycoprotein 1 Receptor or OX40L Receptor or CD134 or TNFRSF4) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (
  • It also reviews key players involved in Tumor Necrosis Factor Receptor Superfamily Member 4 (ACT35 Antigen or TAX Transcriptionally Activated Glycoprotein 1 Receptor or OX40L Receptor or CD134 or TNFRSF4) targeted therapeutics development with respective active and dormant or discontinued projects. (
  • Early studies of CD47 function as a signaling receptor focused on its role in integrin activation, and peptides derived from TSP1 that bind to CD47 were shown to enhance the activation of specific integrins. (
  • CD47 is a 50 kDa membrane receptor that has extracellular N-terminal IgV domain, five transmembrane domains, and a short C-terminal intracellular tail. (
  • CD47 is a high affinity receptor for thrombospondin-1 (TSP-1), a secreted glycoprotein that plays a role in vascular development and angiogenesis, and in this later capacity the TSP1-CD47 interaction inhibits nitric oxide signaling at multiple levels in vascular cells. (
  • CD47 interacts with signal-regulatory protein alpha (SIRPα), an inhibitory transmembrane receptor present on myeloid cells. (
  • CD47 is an antiphagocytic ligand expressed by tumors that binds the inhibitory receptor signal regulatory protein alpha (SIRPα) on phagocytic cells. (
  • CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). (
  • As more experience is gained with the use of genetically engineered chimeric antigen receptor (CAR) T cells in patients with leukemia, the data continue to be highly encouraging. (
  • CAR is an artificial antigen receptor that mediates antibody-targeted recognition. (
  • The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23. (
  • 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. (
  • CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). (
  • 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. (
  • The ubiquitously expressed cell surface glycoprotein CD47 and its receptor signal regulatory protein α (SIRPα) are members of the immunoglobulin superfamily. (
  • CD47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein alpha (SIRPα). (
  • SIRPα is a unique receptor in that it appears to bind CD47 (integrin-associated protein, IAP), a ubiquitously expressed cell surface glycoprotein, rather than MHC ( 8-14 ). (
  • An example of the latter mechanism is that mediated by the cell surface glycoprotein CD47, which by binding to the inhibitory receptor Signal Regulatory Protein alpha (SIRPα) on macrophages, is known to inhibit phagocytosis of viable host cells. (
  • ImmuneOnco takes the advantage of the IP-protected SIRPa-domain to develop the mAb-Trap format by which several bispecific recombinant antibody-receptor proteins have been developed that simultaneously targeting CD47 and other tumor antigen (TA) such as CD20, Her2, PD-L1, new targets, etc. (
  • Myeloid cells contribute to resistance by expressing signal regulatory protein-α (SIRPα), an inhibitory membrane receptor that interacts with ubiquitous receptor CD47 to control macrophage phagocytosis in the tumor microenvironment. (
  • Desmoglein 3 chimeric autoantibody receptor T-cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3, fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B-cell depletion. (
  • In recent years, chimeric antigen receptor (CAR) T cell therapy has made great achievements in the treatment of hematological tumors. (
  • The vector of anti-CD47 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human CD47. (
  • CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells(APC). (
  • However, the CD47-activated SS RBC adhesion receptor(s) that mediated adhesion to immobilized TSP remained unknown. (
  • Here we demonstrate that the α 4 β 1 integrin (VLA-4) is the receptor that mediates CD47-stimulated SS RBC adhesion to immobilized TSP. (
  • These studies therefore identify the α 4 β 1 integrin on SS RBCs as a CD47-activated receptor for TSP, VCAM-1, and plasma fibronectin, revealing novel binding characteristics of this integrin. (
  • The report analyzes the market trends, key medical needs and provides insights into recent advances in the modulation of checkpoint inhibition in the treatment of cancer through the development of fully human monoclonal antibodies, bispecific antibodies, fusion proteins and Chimeric Antigen Receptor (CAR) T cells. (
  • Anti-Human CD47 MAb (Human IgG4) captured on CM5 chip via Anti-Human IgG Fc antibodies surface, can bind Human CD47, His Tag (Cat. (
  • Antibodies targeting the T-cell immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA4) enhance the effectiveness of radiotherapy for melanoma patients, but many remain resistant. (
  • Thus, we propose that treatment of tumor-bearing animals with CD47-blocking antibodies, which are known to inhibit both SIRPα and TSP1 binding to CD47, could directly modulate adaptive as well as innate antitumor immunity. (
  • Agents that block the CD47-SIRPα interaction synergize with pro-phagocytic FcR-activating antibodies, including the anti-CD20 antibody rituximab, for potent phagocytic elimination of tumor cells. (
  • Our bispecific antibodies incorporate a blocking component with weak affinity for CD47, rendering them unable to bind normal cells expressing CD47 alone, and require simultaneous binding to CD20 for high avidity binding to dual antigen-expressing tumor cells. (
  • Such bispecific antibodies targeting CD47 along with tumor-associated antigens may be an effective strategy for selectively eliminating tumor cells that can be broadly applied to cancer. (
  • Early studies showed that some CD47 antibodies can induce apoptosis of T cells. (
  • Additionally, CD47 blocking antibodies inhibit proliferation of unstimulated astrocytoma cells but not normal astrocytes. (
  • However, apoptosis was not observed following culture with other anti-CD47 antibodies. (
  • Here, we use a novel anti-CD47 single domain antibody, derived from an alpaca, in an immunocompetent mouse model of melanoma and find that, in contrast to immunodeficient models, CD47 blockade alone is insufficient to enhance the effects of antimelanoma antibodies. (
  • Interference with the CD47-SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. (
  • While at Stanford, he completed post-doctoral training in the laboratory of Irving Weissman, where he investigated acute myeloid leukemia (AML) stem cells and therapeutic targeting with anti-CD47 antibodies. (
  • Most significantly, we determined that blocking monoclonal antibodies directed against CD47 targeted LSC and depleted leukemia in mouse pre-clinical models. (
  • The researchers found that anti-CD47 antibodies, which can block the "don't-eat-me" signal and enable macrophages to engulf cancer cells, eliminated or inhibited the growth of various blood cancers and solid tumors. (
  • It was completely unexpected that CD8+ T cells would be mobilized when macrophages engulfed the cancer cells in the presence of CD47-blocking antibodies," said MD/PhD student Diane Tseng, the lead author of the study. (
  • Because T cells are sensitized to attack a patient's particular cancer, the administration of CD47-blocking antibodies in a sense could act as a personalized vaccination against that cancer," Tseng added. (
  • Agents that block the CD47-SIRPα interaction can restore phagocytic uptake of CD47 + target cells and lower the threshold for macrophage activation, which can enhance the efficacy of therapeutic antibodies with ADCC-enabling activity. (
  • In summary, the CD47 mAb SRF231 induces robust tumor cell phagocytosis and tumor clearance both alone and in combination with opsonizing antibodies in pre-clinical models of myeloma and lymphoma. (
  • As one of the key targets in the field of anti-tumor immunotherapy, CD47 is regarded by many experts to have the possibility of becoming the next "star" in the field of immuno-oncology following the ground-breaking success of PD1 / PD-L1 antibodies. (
  • Emerging data suggests that CD47 antibody in combination with other treatments, including anti-PD-1 monoclonal antibodies, could result in higher levels of anti-tumor efficacy. (
  • Therapeutic monoclonal antibodies (mAbs), directed towards either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. (
  • We and others have previously demonstrated that inhibiting CD47-SIRPα interactions can substantially potentiate antibody-dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC) of tumor cells by IgG antibodies both in vivo and in vitro. (
  • IgA antibodies are superior in killing cancer cells by neutrophils compared to IgG antibodies with the same variable regions, but the impact of CD47-SIRPα on IgA-mediated killing has not been investigated. (
  • This was shown for multiple tumor types and IgA antibodies against different antigens, i.e. (
  • These findings provide a basis for targeting CD47-SIRPα interactions in combination with IgA therapeutic antibodies to improve their potential clinical efficacy in tumor patients. (
  • The monoclonal antibodies of this invention are antibodies that specifically recognize human Integrin Associated Protein, and the antigens that induce apoptosis of nucleated blood cells having human Integrin Associated Protein. (
  • However, while one cell line of the splenic stromal cells has been established (CF-1 cells) and its cytological characteristics have been studied, specific antibodies that recognize the surface antigens of these cells have never been prepared, nor have their characteristics been elucidated yet in any way. (
  • In light of the aforementioned findings relating to splenic stromal cells and the results of prior research, the present inventors have earnestly made further research aiming at developing specific antibodies that can recognize the splenic stromal cells, made efforts to prepare monoclonal antibodies using the aforementioned splenic stromal cell line as a sensitizing antigen, and finally succeeded in obtaining novel monoclonal antibodies. (
  • Indeed, CD47 blocking antibodies have been found to decrease primary tumor size and/or metastasis in various pre-clinical models. (
  • The present application describes engineered antibodies, with three or more functional antigen binding sites, and uses, such as therapeutic applications, for. (
  • It's well established that cancer cell-expressed CD47 interacts with the NK cell-expressed SIRP family proteins, SIRP alpha and SIRP gamma . (
  • Serial dilutions of Anti-Human CD47 Neutralizing Antibody were added into Human SIRP alpha, His Tag (HPLC-verified) (Cat. (
  • FACS analysis shows that the binding of Human CD47 to ACHN expressing SIRP-a was inhibited by increasing concentration of neutralizing SIRP-a antibody with the IC50 15.02 μg/mL. (
  • TSP1 is the relevant CD47 ligand in T cells because these cells do not express detectable levels of SIRPα ( 13, 14 ). (
  • Indeed, cytotoxic T cells were recently implicated in the antitumor effects of a CD47-blocking antibody, but this outcome was attributed to an indirect effect of inhibiting SIRPα engagement on macrophages ( 23 ). (
  • The interaction of CD47 with signal regulatory protein alpha (SIRPα), a protein on phagocytic cells, transmits a "don't eat me" signal that negatively regulates phagocytosis. (
  • CD47-SIRPα antagonists enable phagocytosis by disrupting the inhibitory signal and can synergize with Fc-mediated pro-phagocytic signals for potent elimination of tumor cells. (
  • A potential limitation of therapeutic CD47-SIRPα antagonists is that expression of CD47 on normal cells may create sites of toxicity or an "antigen sink. (
  • To overcome these limitations and address selective tumor targeting, we developed SIRPabodies to improve the therapeutic benefits of CD47-SIRPα blockade specifically toward tumor. (
  • These findings establish SIRPabodies as a promising approach to deliver the therapeutic benefit of CD47-SIRPα blockade specifically toward tumor cells. (
  • In addition to its lateral association with certain integrins and the Rh complex, three extracellular ligands have been identified for CD47: thrombospondin-1 (TSP1), SIRPα (also known as Src homology 2 domain containing protein tyrosine phosphatase substrate-1 or SHPS1), and SIRPγ. (
  • SIRPs are integral membrane proteins with important signaling functions, and CD47 serves as a counterreceptor for SIRPα. (
  • Most studies of SIRP-CD47 interactions regard CD47 as the ligand that regulates signal transduction through SIRPα (Chao et al. (
  • 2016 ). Mechanistic studies show some involvement of the NO/cGMP cascade and regulation of SIRPα-mediated phagocytosis, but additional pathways have been identified through which CD47 signaling controls mitochondrial-dependent cell death and a protective autophagy response (Soto-Pantoja et al. (
  • 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). (
  • The CD47/SIRPα interaction leads to bidirectional signaling, resulting in different cell-to-cell responses including inhibition of phagocytosis, stimulation of cell-cell fusion, and T-cell activation. (
  • Interruption of CD47-SIRPα interactions in immunodeficient mice bearing human tumors enhances therapeutic antitumor antibody responses by promoting phagocytosis of antibody-bound tumor cells. (
  • CD47 can interact with integrins, Thrombospondin-1 (TSP-1), cell surface gylcoproteins SIRPα and SIRPβ. (
  • CD47 is overexpressed on many cancer cells and binds SIRPα on immune phagocytic cells to produce a "don't eat me" signal. (
  • Immobilized Human SIRP alpha Protein, His Tag at 2 μg/mL (100 μL/well) can bind Biotinylated Human CD47 Protein, Fc Tag with a linear range of 8-250 ng/mL. (
  • CD47 is overexpressed on many cancer cells and binds SIRP? (
  • DSP107 binds CD47 on cancer cells, blocking interaction with SIRP? (
  • The interaction between CD47 and signal regulatory protein alpha (SIRPα), an inhibitory protein expressed on macrophages, prevents phagocytosis of CD47-expressing cells. (
  • SRF231 is a fully human monoclonal antibody that binds with high affinity to human CD47 and blocks the CD47-SIRP▢ interaction. (
  • Both individually and upon their interaction, CD47 and SIRPα have been found to play important role in the homeostasis of T lymphocytes or CD8 - conventional dendritic cells (cDCs) in secondary lymphoid organs. (
  • Both in vitro and in vivo experiments showed that IBI188 can bind to the CD47 antigen on the surface of tumor cells, block the CD47-SIRP? (
  • Increasing evidence suggests that the therapeutic efficacy of these tumor antigen-targeting mAbs is mediated - at least partially - by myeloid effector cells, which are controlled by the innate immune checkpoint interaction between CD47 and SIRPα. (
  • Here, we show that checkpoint inhibition of CD47-SIRPα interactions further enhances destruction of IgA antibody-opsonized cancer cells by human neutrophils. (
  • We conclude that IgA-mediated tumor cell destruction can be further enhanced by CD47-SIRPα checkpoint inhibition. (
  • CD47-SIRPα may represent a potential pathway for the control of hemolytic anemia. (
  • We hypothesized that CD47 might function as a RBC marker of self, and that CD47-deficient cells would therefore be rapidly destroyed by SIRPα−expressing leukocytes. (
  • Although CD47/SIRPα-targeting drugs have been assessed in preclinical models, the therapeutic benefit of selectively blocking SIRPα, and not SIRPγ/CD47, in humans remains unknown. (
  • Selective SIRPα blockade stimulated tumor nest T cell recruitment by restoring murine and human macrophage chemokine secretion and increased anti-tumor T cell responses by promoting tumor-antigen crosspresentation by dendritic cells. (
  • However, nonselective SIRPα/SIRPγ blockade targeting CD47 impaired human T cell activation, proliferation, and endothelial transmigration. (
  • Signal-regulatory protein gamma (SIRPG or SIRP-gamma) is also known as CD172 antigen-like family member B (CD172g), Signal-regulatory protein beta-2 (SIRPB2), is a single-pass type I membrane protein. (
  • Both in vitro and in vivo experiments show 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. (
  • These structures indicate the molecular basis for the fine specificity of SIRP alpha and also to the evolution of antigen receptors. (
  • 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 . (
  • Among them, three have been studied most intensively: cytotoxic T lymphocyte antigen 4 (CTLA4) binding to CD80 or CD86, programmed cell death protein 1 (PD-1) binding to PD-1 ligand 1 (PD-L1) or PD-L2, and SIRPαbinding to CD47. (
  • Recent observations include correlation of central memory immune responses with TB vaccine efficacy, association of SIRP α + cells in ESAT-6:CFP10-elicited multinucleate giant cell formation, early γδ T cell responses to TB, antimycobacterial activity of memory CD4 + T cells via granulysin production, association of specific antibody with antigen burden, and suppression of innate immune gene expression in infected animals. (
  • Phagocytosis assays were performed using tumor targets and inhibition of the CD47-SIRPα pathway drove enhanced uptake. (
  • One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic-"don't eat me"-signal. (
  • Given its essential role as a negative checkpoint for innate immunity and subsequent adaptive immunity, CD47-SIRPα axis has been explored as a new target for cancer immunotherapy and its disruption has demonstrated great therapeutic promise. (
  • The ligation of SIRPα on phagocytes by CD47 expressed on a neighboring cell results in phosphorylation of SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition (ITIM) motifs, leading to the recruitment of SHP-1 and SHP-2 phosphatases. (
  • Thus, CD47-SIRPα interaction functions as a negative immune checkpoint to send a "don't eat me" signal to ensure that healthy autologous cells are not inappropriately phagocytosed. (
  • This report on checkpoint inhibitors provides a detailed analysis of the market based on approved clinical and preclinical developmental candidates that target PD-1/PD-L1, CTLA-4, IDO-1, LAG-3, TIM-3 and CD47/SIRPα. (
  • NOD SIRP-alpha showed enhanced binding to the human CD47 ligand, and its expression on mouse macrophages was required for support of human hematopoiesis. (
  • Macrophage tolerance: CD47-SIRP-alpha-mediated signals matter. (
  • CD47 protects the host cells by suppressing phagocytosis. (
  • CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. (
  • CD47 is a "do not eat me" signal, overexpressed in myeloid malignancies that leads to tumor evasion of phagocytosis by macrophages. (
  • Since then, CD47 has been shown to be overexpressed in multiple hematologic and solid tumor malignancies and appears to be a universal signal by which cancer cells evade the innate immune system, and specifically macrophage phagocytosis ( 3 - 8 ). (
  • The role of CD47 in cancer-mediated evasion of phagocytosis was first described in acute myeloid leukemia (AML) ( 9 ). (
  • However, forced overexpression of CD47 in MOLM13 cells led to dissemination of fulminant leukemia in vivo due to evasion of macrophage phagocytosis. (
  • Owing to these interactions, CD47 plays an important role in lymphocyte homeostasis, maturation and activation of dendritic cells, cellular transmigration and phagocytosis of cells. (
  • A variant of signal regulatory protein alpha (SIRPa) that antagonizes the human cell surface antigen CD47, with potential phagocytosis-inducing, immunostimulating and antineoplastic activities. (
  • This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. (
  • Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate. (
  • The key is using chemotherapy to expose tumors to phagocytosis -- being engulfed and destroyed by innate immune cells that also present antigens from cancer cells to T cells to launch an adaptive immune attack, explains research leader Betty Y.S. Kim, M.D., Ph.D ., associate professor of Neurosurgery . (
  • When the team combined temozolomide with an antibody to block CD47, the combination increased phagocytosis by antigen-presenting macrophages and cleared tumor cells in cell lines. (
  • CD47 on the target cell inhibited LRP1‐mediated phagocytosis of viable cells (e.g. lymphocytes or erythtocytes), but not that of apoptotic cells. (
  • Macrophages play a critical role in fighting cancer through phagocytosis followed by presenting of tumor antigen to T cell. (
  • Mɸ phenotype and cytokine/chemokine production were determined and function assessed via phagocytosis and antigen-presentation assays. (
  • All components of the Canine Leukocyte surface antigen CD47,CD47 ELISA kit should be stored at temperatures between 2 and 8 degrees Celsius. (
  • Canine Leukocyte surface antigen CD47,CD47 ELISA kit antibody storage GENTAUR recommends for long therm storage to freeze at -24 C. For short time storage up to 30 days we suggest fridge storage at 1 to 10 C. Prevent multiple freeze taw cycles of Canine Leukocyte surface antigen CD47,CD47 ELISA kit. (
  • Leukocyte Surface Antigen CD47 - Pipeline Review, H2 2017, outlays comprehensive information on the Leukocyte Surface Antigen CD47 (Antigenic Surface Determinant Protein OA3 or Integrin Associated Protein or Protein MER6 or CD47) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (
  • Leukocyte Surface Antigen CD47 (Antigenic Surface Determinant Protein OA3 or Integrin Associated Protein or Protein MER6 or CD47) - CD47 (Cluster of Differentiation 47) or integrin associated protein (IAP) is a transmembrane protein encoded by the CD47 gene. (
  • The global Leukocyte Surface Antigen CD47 market was valued at million US$ in 2018 and will reach million US$ by the end of 2025, growing at a CAGR of during 2019-2025. (
  • This report focuses on Leukocyte Surface Antigen CD47 volume and value at global level, regional level and company level. (
  • From a global perspective, this report represents overall Leukocyte Surface Antigen CD47 market size by analyzing historical data and future prospect. (
  • For each manufacturer covered, this report analyzes their Leukocyte Surface Antigen CD47 manufacturing sites, capacity, production, ex-factory price, revenue and market share in global market. (
  • Below are the list of possible Leukocyte surface antigen products. (
  • Also known as Leukocyte surface antigen CD47 (Antigenic surface determinant protein OA3) (Integrin-associated protein) (IAP) (Protein MER6) (CD antigen CD47). (
  • Also known as Leukocyte surface antigen CD53 (Cell surface glycoprotein CD53) (CD antigen CD53). (
  • Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. (
  • In T84 cells, the antigen defined by C5/D5 is upregulated by epithelial exposure to IFN-gamma, and represents a membrane glycoprotein of approximately 60 kD that is expressed on the basolateral membrane. (
  • Purification, microsequence analysis, and cross-blotting experiments indicate that the C5/D5 antigen represents CD47, a previously cloned integral membrane glycoprotein with homology to the immunoglobulin superfamily. (
  • CD47 ,or Integrin-associated protein (IAP), is first discovered in a study aimed at studying ype=&key=&min_price=0&max_price=0&sort=goods_id&order=ASC&page=&molecule=812" target="_blank">integrin αvβ3 . (
  • We developed bispecific antibody variants targeting CD47 and CD20 to combine these two functions into a single molecule that recapitulated the potent synergistic effect of combination therapy with no toxic effects on normal cells. (
  • CD47 (CD47 Molecule) is a Protein Coding gene. (
  • Irving Weissman , MD, professor of pathology and of developmental biology , and his team previously showed that nearly all cancers use the molecule CD47 as a "don't-eat-me" signal to escape from being eaten and eliminated by macrophages. (
  • We argue that CD47 is a checkpoint molecule for both innate and adaptive immunity for tumor evasion and is thus a promising target for cancer immunotherapy. (
  • However, CD47 engagement also induces an α 4 β 1 -mediated, RGD-independent adhesion of SS RBCs to immobilized vascular cell adhesion molecule-1 (VCAM-1). (
  • This inhibition of maturation depends on the expression of CD47 on erythrocytes and of its ligand SIRPalpha on DC. (
  • TSP1 is a secreted protein and is the most studied ligand for regulating signaling through CD47. (
  • Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. (
  • Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. (
  • Upon administration, ALX148 binds to CD47 expressed on tumor cells and prevents the interaction of CD47 with its ligand SIRPa, a protein expressed on phagocytic cells. (
  • Like CD172a, the ligand of CD172g is CD47. (
  • Two of the most prominent and promising class of drugs are the immune checkpoint inhibitors, that target the proteins found on T-lymphocytes or T cells such as programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathways. (
  • The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. (
  • Macrophages are a key cell type in the innate immune response with CD47 being identified as a dominant macrophage checkpoint. (
  • CD47 (also known as integrin associated protein) is a transmembrane protein that mainly functions as an anti-phagocytic or "do not eat me" signal, enabling CD47-expressing cells to evade phagocytic elimination by macrophages and other phagocytes. (
  • The research revives interest in an aspect of macrophages that has been neglected for decades: their role in presenting antigens to T cells. (
  • For many years, researchers have focused on the dendritic cell as the main antigen-presenting cell, and have generally believed that macrophages specialize in degrading antigens rather presenting them. (
  • This research shows that macrophages can be effective at antigen presentation and are powerful initiators of the CD8+T cell response. (
  • Analyzing mouse and human glioblastoma lines, Kim and colleagues found heavy expression on the cell surface of CD47, which sends a conflicting signal to immune macrophages: "don't eat me. (
  • Data suggest a reduction in the CD47 antigen (show CD47 ELISA Kits )/ signal-regulatory protein alpha (SIRPalpha) pathway by programmed cell death protein 1 (PD-1 (show PDCD1 ELISA Kits )) blockade, which regulates Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). (
  • Loss of cell surface CD47 (show CD47 ELISA Kits ) clustering formation and binding avidity to SIRPalpha facilitate apoptotic cell clearance by macrophages. (
  • Red blood cells that lacked CD47 were rapidly cleared from the bloodstream by splenic red pulp macrophages. (
  • Thus, macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign. (
  • The studies of the present thesis aimed at investigating possible changes to CD47 on apoptotic cells, which could influence their elimination by macrophages. (
  • Human melanoma data from The Cancer Genome Atlas revealed positive correlations between CD47 mRNA expression and expression of T-cell regulators including CTLA4 and its counter receptors CD80 and CD86. (
  • This chapter discusses selected scavenger and lectinlike antigen-presenting cell (APC) receptors in relation to innate immunity to illustrate principles and provide questions for further study. (
  • ACROBiosystems provides a unique set of CD47-relevant products, including mutilple avi tag pre-biotinylated proteins, for rapid high throughput screening. (
  • 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 αvβ3 integrin and trimeric G proteins. (
  • Human antigen binding proteins that bind .beta. (
  • The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. (
  • Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. (
  • Correspondingly, the treatment of locally irradiated B16F10 melanomas in C57BL/6 mice using combined blockade of CD47 and CTLA4 significantly increased the survival of mice relative to either treatment alone. (
  • These data suggest that combining CTLA4 and CD47 blockade could provide a survival benefit by enhancing adaptive T- and NK-cell immunity in irradiated tumors. (
  • Vonderheide RH (2015) CD47 blockade as another immune checkpoint therapy for cancer. (
  • CD47 blockade has been found to confer radioprotection to normal tissues while enhancing tumor radiosensitivity. (
  • Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8 + T cells. (
  • Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell-deficient mice, whereas adoptive transfer of tumor-specific CD8 + T cells restored combinatorial efficacy. (
  • CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8 + CTL-mediated tumor cell killing in vitro . (
  • We previously demonstrated that blockade of CD47 enhances the radiation-induced delay in tumor growth in two syngeneic mouse models ( 24 ). (
  • Blockade of CD47 leads to engulfment of leukemic cells and therapeutic elimination. (
  • Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. (
  • In this review, we highlight the various functions of CD47, discuss anti-tumor responses generated by both the innate and adaptive immune systems as a consequence of administering anti-CD47 blocking antibody, and finally elaborate on the clinical potential of CD47 blockade. (
  • We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. (
  • CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. (
  • In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. (
  • The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. (
  • Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer. (
  • Antisense suppression of CD47 on human T cells in vitro using a translational blocking morpholino (CD47 m) alone or combined with anti-CTLA4 enhanced antigen-dependent killing of irradiated melanoma cells. (
  • Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8 + T cells in a CD47-deficient microenvironment, with an associated increase in T cell-dependent intratumoral expression of granzyme B. Correspondingly, an inverse correlation between CD8 + T-cell infiltration and CD47 expression was observed in human melanomas. (
  • Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8 + cytotoxic T cells, with the potential to increase curative responses. (
  • Correspondingly, elevated CD47 expression on cancer cells is proposed to suppress antitumor innate immunity ( 4, 5 ). (
  • Binding of the C-terminal signature domain of TSP1 to CD47 causes a profound inhibition of the nitric oxide/cGMP signaling in vascular cells and T cells ( 6-8 ). (
  • In the immune system binding of TSP1 to CD47 inhibits T-cell activation ( 9-11 ), in part, by inhibiting the autocrine activating function of hydrogen sulfide signaling in T cells ( 12 ). (
  • CD47 is highly expressed on a variety of tumor cells. (
  • SIRPabodies selectively bound to dual antigen-expressing tumor cells in the presence of a large antigen sink. (
  • Here, we have studied the response of breast cancer cells to CD47 ligands TSP-1, the CD47 agonist peptide 4N1K derived from TSP-1, and the anti-CD47 monoclonal antibody 1F7. (
  • Thus, CD47-mediated killing of breast cancer cells occurs by a novel pathway involving regulation of cAMP levels by heterotrimeric Gi with subsequent effects mediated by PKA. (
  • CD47 was first identified in 1987 as an antigen that is missing in red blood cells of patients with Rhesus (Rh)-null hemolytic anemia (see the following reviews for CD47 source references unless otherwise cited: Rogers et al. (
  • 2013 ). Loss of CD47 is not the primary cause of this disease, but CD47 closely associates with the Rh complex on red blood cells. (
  • TSP1 binding to CD47 inhibited NO-mediated activation of soluble guanylate cyclase (sGC) in endothelial cells, and this inhibitory effect was lost in endothelial cells from CD47 -null mice. (
  • 2012 ). Thus, CD47 signaling is now recognized as a highly redundant inhibitor of the canonical NO/cGMP signaling cascade in vascular cells. (
  • CD47 is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells. (
  • Activation of CD47 with TSP-1 increases proliferation of human U87 and U373 astrocytoma cells but not normal astrocytes. (
  • Though the exact mechanism is unclear, it is likely that CD47 promotes proliferation via the PI3K/Akt pathway in cancerous cells but not normal cells. (
  • Loss of CD47 allows sustained proliferation of primary murine endothelial cells and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. (
  • Expression of several stem cell markers, including c-Myc, is elevated in CD47-null endothelial cells and a human T cell line lacking CD47. (
  • Activation of CD47 with TSP-1 in wild-type cells inhibits proliferation and reduces expression of stem cell transcription factors. (
  • The activation of CD47 induces rapid apoptosis of T cells. (
  • Similarly, CD47 ligation rapidly induces apoptosis in B-cell chronic lymphocytic leukemia (CLL) cells. (
  • Treatment with a disulfide-linked antibody dimer induces apoptosis of CD47-positive primary B-CLL and leukemic cells (MOLT-4 and JOK-1). (
  • The expression of CD47 varies in different tissue types depending upon the cytoplasmic tail isoform associated, for e.g the 16 amino acid form 2, is expressed in all cells of hematopoietic origin, endothelial and epithelial cells whereas 36 amino acids form 4 is expressed mainly in neurons, intestine, and testis. (
  • Overlay histogram showing flow cytometric analysis of CD47 knockout cells. (
  • Wild type (red) and knockout cells (blue) were stained with CD47-PE (REA220). (
  • ICC/IF analysis of U2OS cells using CD47 antibody (red) and DAPI (blue). (
  • Elevated postinjury thrombospondin 1-CD47 triggering aids differentiation of patients' defective inflammatory CD1a+dendritic cells. (
  • We have focused on one of these markers, CD47, that contributes to leukemia development by blocking the ingestion and removal of leukemia cells by cells of the immune system. (
  • The Menlo Park, CA-based company takes its name from the CD47 protein on cancer cells that its drugs target. (
  • DSP107 targets CD47-overexpressing tumors, simultaneously blocking macrophage inhibitory signals and delivering an immune costimulatory signal to tumor antigen-specific, activated T-cells. (
  • LSCs possess surface antigen profiles and signal transduction activation profiles which may allow differential targeting as compared with normal hematopoietic stem cells. (
  • Nevertheless, CHO cells also expressed hamster CD47 which might contribute to sCD23 binding to αv/CD51 on live cells as reported for Vn binding to untransfected CHO cells (Lindberg et al. (
  • In addition, blocking CD47 signaling activates both an anti-tumor cytotoxic T-lymphocyte (CTL) immune response and T-cell-mediated killing of CD47-expressing tumor cells. (
  • CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. (
  • Current approaches to developing the vaccines rely on using immune cells called dendritic cells to introduce cancer protein fragments to T cells - a process known as antigen presentation. (
  • The fact that T cells become involved in fighting cancer as a result of CD47-blocking antibody therapy could have important clinical implications. (
  • CD47 is also expressed at low levels on virtually all non-malignant cells, and loss of expression or changes in membrane distribution may serve as markers of aged or damaged cells, particularly on red blood cells (RBC). (
  • CD47 (show CD47 ELISA Kits ), TSP1 (show THBS1 ELISA Kits ), and to a lesser extent SIRPalpha facilitate exosome-mediated myeloid-derived suppressor cells chemotaxis and migration. (
  • Treg cells protect dopaminergic neurons against MPP + neurotoxicity by a cell-to-cell contact mechanism underlying CD47 (show CD47 ELISA Kits )- SIRPA interaction and Rac1 / Akt (show AKT1 ELISA Kits ) activation. (
  • Here we show that CD47 (integrin-associated protein) functions as a marker of self on murine red blood cells. (
  • In contrast to MHC, CD47 is present also on red blood cells (RBCs). (
  • Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. (
  • On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. (
  • However cancer cells are smart and can always find a way to evade the surveillance, such as by over-expressing immune checkpoints including CD47. (
  • CD47 expression is hijacked by cancer cells to evade immune surveillance and macrophage-mediated removal. (
  • Expression of the CD47 epitope was confirmed on PMN and was also localized to the basolateral membrane of normal human colonic epithelial cells. (
  • The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-CD47 antibody linked to a CD28 transmembrane domain/ endodomain and CD3-zeta signaling domains. (
  • We recently reported that CD47 (integrin-associated protein) on sickle red blood cells (SS RBCs) activates G-protein-dependent signaling, which promotes cell adhesion to immobilized thrombospondin (TSP) under relevant shear stress. (
  • Graft failure in the transplantation of hematopoietic stem cells occurs despite donor-host genetic identity of human leukocyte antigens, suggesting that additional factors modulate engraftment. (
  • Signaling through CD47 also regulates T-cell differentiation and adhesion as well as natural killer (NK) and dendritic cell functions that regulate adaptive immunity ( 15-22 ). (
  • 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 triggering during Cnt MDDC differentiation increased SHP-1 activation, inhibiting IL-4-induced STAT-6 activation (critical for CD1a(+)MDDC differentiation). (
  • Forskolin, 8-bromo cAMP, and isobutylmethylxanthine (IBMX) all prevented CD47-mediated apoptosis, indicating the involvement of cAMP. (
  • Epidermal growth factor also inhibited CD47-induced apoptosis via a PKC-dependent but ERK-independent pathway. (
  • Binding of TSP-1 to CD47 influences several fundamental cellular functions including cell migration and adhesion, cell proliferation or apoptosis, and plays a role in the regulation of angiogenesis and inflammation. (
  • CD47 ligation leads to cell death in many normal and tumor cell lines via apoptosis or autophagy. (
  • The apoptosis inducing function of CD47 appears to be dependent on activation of specific epitopes on the extracellular domain. (
  • 1993). To directly assess whether CD47 expression was required for sCD23 interaction with αv/CD51, we examined sCD23 binding to human CD47 deficient cell lines. (
  • CD47 signaling induces an "inside-out" activation of α 4 β 1 on SS RBCs as indicated by an RGD-dependent interaction of this integrin with soluble, plasma fibronectin. (
  • The transmembrane protein CD47 is an immunoglobulin superfamily member involved in multiple cellular processes, including cell migration, adhesion and T cell function. (
  • Each antibody is crafted with care according to rigorous protocols for immunogen design and preparation, presentation to host animal, and high-affinity purification against the antigen. (
  • On binding with CD47, CD172g mediates cell-cell adhesion. (
  • CD47 mediates post-adhesive events required for neutrophil migration across polarized intestinal epithelia. (
  • The purity of Human CD47, Fc Tag (HPLC-verified) (Cat. (
  • No. SIA-H5225 ) at 2 μg/mL (100 μL/well) can bind Biotinylated Human CD47, Fc,Avitag (Cat. (
  • FACS assay shows that Human CD47, Fc Tag (HPLC-verified) (Cat. (
  • Immobilized Anti-CD47 MAb, Human IgG4 at 2 μg/mL (100 μL/well) can bind Biotinylated Human CD47, His,Avitag (Cat. (
  • No. SIA-H5225): Biotinylated Human CD47, Fc,Avitag (Cat. (
  • The concentration of Human CD47 used is 10 μg/mL. (
  • CD47 Monoclonal antibody specifically detects CD47 in Human, Mouse samples. (
  • CD47 was first identified as a tumor antigen on human ovarian cancer in the 1980s ( 2 ). (
  • In initial studies, CD47 was found to be overexpressed in both mouse and human AML compared to normal cell counterparts and its upregulation was directly tied to disease pathogenesis via macrophage evasion ( 3 , 9 ). (
  • To the later point, a human CD47-negative AML cell line (MOLM13) was unable to establish disseminated disease in a xenograft mouse transplant model ( 9 ). (
  • With Dr. Weissman, he developed a humanized anti-CD47 antibody, initiated first-in-human clinical trials. (
  • The Stanford group plans to start human clinical trials of the anti-CD47 cancer therapy in 2014. (
  • Biotinylated Recombinant Human CD47 (Gln 19 - Pro 139) fused with human IgG1 Fc fragment at the C-terminus, followed by an Avi tag was expressed in HEK293. (
  • Recombinant Human CD47 produced by transfected human cell is a secreted protein with sequence (Gln19Pro139) of Human CD47 fused with a polyhistidine tag at the Cterminus. (
  • CD47 was originally identified as a tumor antigen on human ovarian cancer and was subsequently shown to be expressed on multiple human tumor types, including both hematologic and solid tumors. (
  • Systemic sclerosis is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen locus. (
  • However, the functional relationship between human leukocyte antigen gene(s) and disease development remains unknown. (
  • Three essential tools developed in cattle and used for the control of human tuberculosis (TB) include (1) vaccination with an attenuated Mycobacterium bovis Bacillus Calmette Guerin (BCG, [ 1 ]), (2) use of tuberculin as an in vivo diagnostic reagent, and (3) antigen-induced interferon- (IFN-) γ as an in vitro biomarker of TB infection. (
  • CD47 is a 50 KDa heavily glycosylated protein with an extracellular IgV domain, five transmembrane domains and a cytoplasmic tail, which exists in 4 different isoforms. (
  • Chao MP, Weissman IL, Majeti R (2012) The CD47-SIRPalpha pathway in cancer immune evasion and potential therapeutic implications. (
  • Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy. (
  • The current pipeline includes an immune-oncology program targeting CD47/QPCTL and druggable modifiers of NP-C1 (Niemann Pick disease, type C) and Barth syndrome, both rare metabolic disorders. (
  • Its lead candidates include an immune-oncology program targeting CD47/QPCTL, and two rare diseases programs based on druggable modifiers of NP-C1 (Niemann Pick disease, type C), a rare lipid storage disorder that affects lipid metabolism, or the way fats, lipids, and cholesterol are stored in or removed from your body, and Barth syndrome, an X-linked disorder also of lipid metabolism that affects the heart. (
  • High expression of CD47 on tumors blocks phagocytic uptake, subsequent antigen cross-presentation and T cell activation, which collectively contribute to tumor immune evasion. (
  • In this study, the investigators will investigate the protein expression of several specific molecules in immune checkpoint pathways such as PD-L1, PD-L2 and CD47 in the large neurological resection specimens by immunohistochemical staining of patients with CNSL. (
  • The adoption of protein expression of immune checkpoint pathways (CTLA-4, PD-L1, PD-L2, CD47) as a prognostic factor in patients with PCNSL. (
  • Is CD47 an innate immune checkpoint for tumor evasion? (
  • The activity of this CAR-T cell is controlled by a tumor antigen-specific based on dose of Fab, thus providing a fully controllable immune response. (
  • CD47 m alone or in combination with anti-CTLA4 increased CD3 + T-cell infiltration in irradiated tumors. (
  • Primary AML patient samples displayed increased expression of CD47 on the cell surface compared to normal cell counterparts ( 3 ). (
  • A population of CD3-positive lymphocytes expressing the CD56 surface antigen, with potential immunomodulating activity. (
  • Thus, CD47 represents a potential new therapeutic target for downregulating active inflammatory disease of mucosal surfaces. (
  • The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. (
  • Clone REA170 recognizes CD47, which is also known as integrin-associated protein. (
  • CD47+ and CD47− cell lines were stained with two anti-CD47 mAbs (clone 10G2 and B6H12), anti-αv (CD51) and anti-β3 (CD61) mAbs, or B-sCD23 as described in Materials and Methods. (
  • sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. (
  • The ready-to-use lentiviral particles of Lenti-CD47 CAR (scFv-28εRIγ, B6H12.2)-VP is packaged using 3rd generation of lentiviral packaging system, in which the gene of CAR will be driven by a CMV promotor. (
  • As with neo-antigen cancer vaccines, CD47 blockers are one way drug developers hope to expand the reach of immunotherapy. (
  • Anti-CTLA4 combined with CD47 m resulted in the greatest increase in intratumoral granzyme B, interferon-γ, and NK-cell marker mRNA expression. (
  • In CD47-deficient syngeneic hosts, engrafted B16 melanomas were 50% more sensitive to irradiation, establishing that CD47 expression in the microenvironment was sufficient to limit tumor radiosensitivity. (
  • The clinical relevance of CD47 expression was then evaluated in AML patients. (
  • Furthermore, higher levels of CD47 mRNA expression was an independent poor prognostic factor in AML patients. (
  • Due to the ubiquitous expression of CD47, signaling differs according to cell type. (
  • In many hematologic cancers, high CD47 expression is associated with poor clinical outcomes. (
  • These results indicate that irinotecan may enhance the effect of T cell activation caused by anti -PD-L1 treatment by reducing Tregs and augmenting MHC class I -mediated tumor antigen presentation, and concurrent upregulation of PD-L1 expression can be blocked by the anti -PD-L1 antibody . (
  • To fulfill this aim, the protein expression of CTLA-4, PD-L1, PD-L2, and CD47 in the neurosurgical resection specimens of patients with PCNSL will be evaluated by immunohistochemistry (IHC) techniques. (
  • Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. (
  • This review will describe the role of CD47 in myeloid malignancies and pre-clinical data supporting CD47 targeting. (
  • CD47, originally named integrin-associated protein (IAP), is a 50kDa protein containing five membrane-spanning sequences and a short cytoplasmic tail. (
  • CD47 is a type I integral membrane protein with an extracellular immunoglobulin variable (IgV)-like domain, five membrane-spanning segments, and a short alternatively spliced carboxy-terminal cytoplasmic tail. (
  • There are four alternatively spliced isoforms of CD47 that differ only in the length of their cytoplasmic tail. (
  • However, these isoforms are highly conserved between mouse and man, suggesting an important role for the cytoplasmic domains in CD47 function. (
  • evidence of the highly conserved nature of the isoforms between mouse and man, suggests an important role for the cytoplasmic domains in CD47 function. (
  • CD47 signaling in SS RBCs appears to be independent of large scale changes in cAMP formation but nonetheless promotes α 4 β 1 -mediated adhesion via a protein kinase A-dependent, serine phosphorylation of the α 4 cytoplasmic domain. (
  • Followup studies has established CD47 as the quintessential "marker of self" expressed in all cell types. (
  • This CD47-mediated cell death did not require active caspases or Bcl-2 degradation and did not cause DNA laddering or cytochrome c release. (
  • Ligation of CD47 by these peptides in different cell types also stimulated calcium influx and changes in cAMP levels, MAP kinase activities, and Giα activation. (
  • A second major function of CD47 signaling is to control cell survival. (
  • These interactions result in CD47/integrin complexes that affect a range of cell functions including adhesion, spreading and migration. (
  • The role of CD47 in promoting cell proliferation is heavily dependent on cell type as both activation and loss of CD47 can result in enhanced proliferation. (
  • Product Quality tested by: Transient overexpression cell lysate was tested with Anti-CD47 antibody by Western Blots. (
  • WB analysis of extracts from various cell lines using CD47 antibody. (
  • Increased pSHP-1, decreased antigen processing, and depressed T cell stimulation characterized Pt Dysf DC. (
  • Binding of sCD23 to CD47+ and CD47− cell lines. (
  • As shown in Fig. 8, sCD23 bound to OV10 ovarian carcinoma VnR+/CD47− cell line demonstrating that CD47 was dispensable for sCD23 binding. (
  • A proprietary agent that targets the cancer stem cell (CSC) antigen CD44, with potential antineoplastic activity. (
  • CD47 is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. (
  • T cell co-cultures were also performed to assess effects on antigen-presentation. (
  • A novel CAR-T cell therapy (called SmarT-cell) that simultaneously targets three antigens (PSCA, TGF, and IL4), was discovered. (
  • It transmits an activation signal to the T cell after antigen is bound. (
  • Indeed, Anti-CD47 mAb has been demonstrated to reduce the atherosclerotic burden in several in vivo models. (
  • This is the fourth IND approval the company has received this year, including anti-CTLA-4 mAb, anti-RANKL mAb, anti-OX40 mAb and anti-CD47 mAb. (