SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions. 2010

Cynthia Detre, and Marton Keszei, and Xavier Romero, and George C Tsokos, and Cox Terhorst
BIDMC Division of Immunology, Harvard Center for Life Sciences, Rm. CLS 938, 3 Blackfan Circle, Boston, MA 02115, USA. cdetre@bidmc.harvard.edu

One or more of the signaling lymphocytic activation molecule (SLAM) family (SLAMF) of cell surface receptors, which consists of nine transmembrane proteins, i.e., SLAMF1-9, are expressed on most hematopoietic cells. While most SLAMF receptors serve as self-ligands, SLAMF2 and SLAMF4 use each other as counter structures. Six of the receptors carry one or more copies of a unique intracellular tyrosine-based switch motif, which has high affinity for the single SH2-domain signaling molecules SLAM-associated protein and EAT-2. Whereas SLAMF receptors are costimulatory molecules on the surface of CD4+, CD8+, and natural killer (NK) T cells, they also involved in early phases of lineage commitment during hematopoiesis. SLAMF receptors regulate T lymphocyte development and function and modulate lytic activity, cytokine production, and major histocompatibility complex-independent cell inhibition of NK cells. Furthermore, they modulate B cell activation and memory generation, neutrophil, dendritic cell, macrophage and eosinophil function, and platelet aggregation. In this review, we will discuss the role of SLAM receptors and their adapters in T cell function, and we will examine the role of these receptors and their adapters in X-linked lymphoproliferative disease and their contribution to disease susceptibility in systemic lupus erythematosus.

UI MeSH Term Description Entries
D008180 Lupus Erythematosus, Systemic A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Libman-Sacks Disease,Lupus Erythematosus Disseminatus,Systemic Lupus Erythematosus,Disease, Libman-Sacks,Libman Sacks Disease
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008232 Lymphoproliferative Disorders Disorders characterized by proliferation of lymphoid tissue, general or unspecified. Duncan's Syndrome,X-Linked Lymphoproliferative Syndrome,Duncan Disease,Epstein-Barr Virus Infection, Familial Fatal,Epstein-Barr Virus-Induced Lymphoproliferative Disease In Males,Familial Fatal Epstein-Barr Infection,Immunodeficiency 5,Immunodeficiency, X-Linked Progressive Combined Variable,Lymphoproliferative Disease, X-Linked,Lymphoproliferative Syndrome, X-Linked, 1,Purtilo Syndrome,X-Linked Lymphoproliferative Disease,X-Linked Lymphoproliferative Disorder,Disease, Duncan,Disease, X-Linked Lymphoproliferative,Diseases, X-Linked Lymphoproliferative,Disorder, Lymphoproliferative,Disorder, X-Linked Lymphoproliferative,Disorders, Lymphoproliferative,Disorders, X-Linked Lymphoproliferative,Epstein Barr Virus Induced Lymphoproliferative Disease In Males,Epstein Barr Virus Infection, Familial Fatal,Familial Fatal Epstein Barr Infection,Immunodeficiency 5s,Immunodeficiency, X Linked Progressive Combined Variable,Lymphoproliferative Disease, X Linked,Lymphoproliferative Diseases, X-Linked,Lymphoproliferative Disorder,Lymphoproliferative Disorder, X-Linked,Lymphoproliferative Disorders, X-Linked,Lymphoproliferative Syndrome, X-Linked,Lymphoproliferative Syndromes, X-Linked,Purtilo Syndromes,Syndrome, Purtilo,Syndrome, X-Linked Lymphoproliferative,Syndromes, Purtilo,Syndromes, X-Linked Lymphoproliferative,X Linked Lymphoproliferative Disease,X Linked Lymphoproliferative Disorder,X Linked Lymphoproliferative Syndrome,X-Linked Lymphoproliferative Diseases,X-Linked Lymphoproliferative Disorders,X-Linked Lymphoproliferative Syndromes
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071177 Signaling Lymphocytic Activation Molecule Family Member 1 A 70-kDa SLAM family receptor that consists of an extracellular IMMUNOGLOBULIN-LIKE DOMAIN and an IMMUNOGLOBULIN C2-SET DOMAIN. It is expressed primarily by THYMOCYTES and activated T-LYMPHOCYTES, as well as by MACROPHAGES and DENDRITIC CELLS. It binds SLAMF1 receptors on other cells to mediate T-cell maturation and proliferation. It is also a receptor for the MEASLES VIRUS. CD150 Antigen,CDw150 Protein,SLAM Protein,SLAM Receptor,SLAMF1 Protein,SLAMF1 Receptor,Antigen, CD150
D000071179 Signaling Lymphocytic Activation Molecule Associated Protein A signal transducing adaptor protein that contains a single SH2 DOMAIN and is essential for the regulation of SLAM FAMILY RECEPTORS in the immune response. Mutations in the SLAM-associated protein gene have been identified in cases of X-LINKED LYMPHOPROLIFERATIVE DISEASE. SH2D1A Protein,SLAM-Associated Protein,SLAM Associated Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013601 T-Lymphocytes 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. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte

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