SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions.
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.
BIDMC Division of Immunology, Harvard Center for Life Sciences, Rm. CLS 938, 3 Blackfan Circle, Boston, MA 02115, USA. cdetre@bidmc.harvard.edu
Cynthia
C
Detre
Marton
M
Keszei
Xavier
X
Romero
George C
GC
Tsokos
Cox
C
Terhorst
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; C000604059:SLAMF1 protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1