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

Abstract

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 Tcell 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.

Wild-Type Measles Virus Interferes with Short-Term Engraftment of Human CD34 + Hematopoietic Progenitor Cells

“…The Ig superfamily member CD150 (also referred to as SLAMF1) is the type species of the SLAM (signaling lymphocytic activation molecule) family (SLAMF), which consists of 9 proteins that are expressed on most hematopoietic cells and are activated to signal on homo-or heterotypic interactions (9). Within this family, CD150 seems to be unique in acting both as an MV uptake receptor and a general microbial sensor (2).…”

SAP Facilitates Recruitment and Activation of LCK at NTB-A Receptors during Restimulation-Induced Cell Death

“…Recently, the clinical significance of this process was underscored in patients with X-linked lymphoproliferative disease (XLP) (4)(5)(6). Most cases of XLP are linked to mutations or deletions in SH2D1A, which encodes the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) (7).…”

SAP expression in invariant NKT cells is required for cognate help to support B-cell responses

“…7,8 Mutations of the SH2D1A gene, encoding the signaling lymphocyte activation molecule (SLAM) associated protein (SAP), impair T cell-dependent humoral responses in patients with X-linked lymphoproliferative syndrome (XLP), as well as in SAP Ϫ/Ϫ mice. [9][10][11][12] In addition to this defect of conventional CD4 ϩ T cells affecting T follicular helper cell-B cell interactions, both XLP patients and SAP Ϫ/Ϫ mice have reduced numbers of NKT cells. [13][14][15] NKT cells develop in the cortex of the thymus as a result of homotypic interactions between thymocyte precursors carrying the NKT cell-specific ␣␤TCR with thymocytes expressing CD1d/ligands.…”