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

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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 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.

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Acknowledgements

We are grateful for support from the NIH (AI-15066, AI-076210, AI-065687 to CT) and the CCFA (to XR).

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Authors and Affiliations

  1. BIDMC Division of Immunology, Harvard Center for Life Sciences, Rm. CLS 938, 3 Blackfan Circle, Boston, MA, 02115, USA

    Cynthia Detre, Marton Keszei, Xavier Romero & Cox Terhorst

  2. BIDMC Division of Rheumatology, Harvard Center for Life Sciences, Rm. CLS 937, 3 Blackfan Circle, Boston, MA, 02115, USA

    George C. Tsokos

  3. Harvard Medical School, Boston, MA, USA

    Cox Terhorst

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  1. Cynthia Detre
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Correspondence to Cynthia Detre or Cox Terhorst.

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Detre, C., Keszei, M., Romero, X. et al. SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions. Semin Immunopathol 32, 157–171 (2010). https://doi.org/10.1007/s00281-009-0193-0

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