Molecular and immunological basis of X-linked lymphoproliferative disease

Authors

  • Sylvain Latour,

    1. Authors' addresses
      1Unité INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.2Laboratory of Molecular Oncology, IRCM, the Department of Medicine, University of Montreal, and the McGill Cancer Center and Departments of Biochemistry, Medicine, and Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
    Search for more papers by this author
  • André Veillette

    1. Authors' addresses
      1Unité INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.2Laboratory of Molecular Oncology, IRCM, the Department of Medicine, University of Montreal, and the McGill Cancer Center and Departments of Biochemistry, Medicine, and Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
    Search for more papers by this author

Sylvain Latour
Unité INSERM U429
Hôpital Necker Enfants-Malades
149 rue de Sèvres
75015 Paris
France
Tel.: 33 1 44 49 50 51
Fax: 33 1 42 73 06 40
e-mail: latour@necker.fr
André Veillette
IRCM
110 Pine Ave West
Montréal, Québec
Canada
HZW 1R7
Tel.: 1 514 987 5561
Fax: 1 514 987 5562
e-mail: veillea@ircm.qc.ca

Abstract

Summary:  X-linked lymphoproliferative (XLP) disease is a human immune dysfunction characterized primarily by an inappropriate response to Epstein–Barr virus infection. In 1998, it was discovered that XLP is caused by inactivating mutations in the SAP/SH2D1A/DSHP gene. This gene codes for an immune cell-specific polypeptide termed SAP (SLAM-associated protein) that is composed almost exclusively of an Src homology 2 (SH2) domain. By way of its SH2 domain, SAP interacts with tyrosine-based motifs located in the cytoplasmic region of members of the SLAM (signaling lymphocyte activation molecule) family of receptors. Recent findings indicate that SAP is required for the function of SLAM-related receptors, as a consequence of its capacity to promote the recruitment and activation of the Src-related protein tyrosine kinase FynT, thereby allowing SLAM receptor-mediated protein tyrosine phosphorylation signals in immune cells. Functional and genetic analyses suggest that the phenotype associated with XLP is caused in large part by defects in the functions of SLAM-related receptors due to SAP deficiency.

Ancillary