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

Author

Listed:
  • J. Sayos

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • C. Wu

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • M. Morra

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • N. Wang

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • X. Zhang

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • D. Allen

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • S. van Schaik

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • L. Notarangelo

    (University of Brescia)

  • R. Geha

    (The Children's Hospital, Harvard Medical School)

  • M. G. Roncarolo

    (Cellular Therapy Laboratory, Telethon Institute for Gene Therapy)

  • H. Oettgen

    (The Children's Hospital, Harvard Medical School)

  • J. E. De Vries

    (Novartis Forschungsinstitut Geselschaft mbH)

  • G. Aversa

    (Novartis Forschungsinstitut Geselschaft mbH)

  • C. Terhorst

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

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 CDw150), 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.

Suggested Citation

  • 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, 1998. "The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM," Nature, Nature, vol. 395(6701), pages 462-469, October.
    • Handle: RePEc:nat:nature:v:395:y:1998:i:6701:d:10.1038_26683
    DOI: 10.1038/26683
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