The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM

J. Sayos, C. Wu, M. Morra, N. Wang, X. Zhang, D. Allen, S. Van Schaik, L. Notarangelo, R. Geha, M. G. Roncarolo, H. Oettgen, J. E. De Vries, G. Aversa, C. Terhorst

Research output: Contribution to journalArticlepeer-review

Abstract

In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw 150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell- specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tail, acts as an inhibitor by blocking recruitment of the SH2-domain- containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein- Barr virus infections.

Original languageEnglish
Pages (from-to)462-469
Number of pages8
JournalNature
Volume395
Issue number6701
DOIs
Publication statusPublished - Oct 1 1998

ASJC Scopus subject areas

  • General

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