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

Nature volume 395, pages 462–469 (1998)Cite this article

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.

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Acknowledgements

We thank J. David, J. Fingeroth and N. Letvin for critically reviewing the manuscript; J. Sumegi for sharing unpublished data; N. van Orsouw and J. Vijg for guidance in analysing PCR products; and E. Wang, M. Comiskey, A. Bywater and A. Hren for technical assistance. This work was supported by a grant from the NIH. J.S. is supported by a fellowship from the Ministerio de Educacion y Cultura de España.

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Authors and Affiliations

  1. Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, Massachusetts, USA
    J. Sayos, C. Wu, M. Morra, N. Wang, X. Zhang, D. Allen, S. van Schaik & C. Terhorst
  2. Department of Pediatrics, University of Brescia, Brescia, 25125, Italy
    L. Notarangelo
  3. Division of Immunology, The Children's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA
    R. Geha & H. Oettgen
  4. Cellular Therapy Laboratory, Telethon Institute for Gene Therapy, Milan, 20132, Italy
    M. G. Roncarolo
  5. Novartis Forschungsinstitut Geselschaft mbH, Vienna, A-1235, Austria
    J. E. De Vries & G. Aversa

Authors

  1. J. Sayos
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  2. C. Wu
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  3. M. Morra
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  4. N. Wang
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  5. X. Zhang
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  6. D. Allen
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  7. S. van Schaik
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  8. L. Notarangelo
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  9. R. Geha
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  10. M. G. Roncarolo
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  11. H. Oettgen
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  12. J. E. De Vries
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  13. G. Aversa
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  14. C. Terhorst
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Correspondence toJ. Sayos or C. Terhorst.

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Sayos, J., Wu, C., Morra, M. et al. The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM.Nature 395, 462–469 (1998). https://doi.org/10.1038/26683

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