Differential role of SLP-76 domains in T cell development and function

Lalit Kumar, Vadim Pivniouk, Miguel A. De La Fuente, Dhafer Laouini, Raif S. Geha

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The adapter SLP-76 is essential for thymocyte development. SLP-76-/- mice were reconstituted with SLP-76 deletion mutant transgenes to examine the role of SLP-76 domains in T cell development and function. The N-terminal domain deletion mutant completely failed to restore thymocyte development. Mice reconstituted with Gads-binding site and SH2 domain deletion mutants had decreased thymic cellularity, impaired transition from double to single positive thymocytes, and decreased numbers of mature T cells in the spleen. Calcium mobilization and extracellular signal-regulated protein kinase activation were decreased in the Gads-binding site mutant but almost normal in the SH2 domain mutant. T cells from both mutants failed to proliferate following T cell antigen receptor ligation. Nevertheless, both mutants mounted partial cutaneous hypersensitivity responses and normal T cell dependent IgG1 antibody responses. These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions.

Original languageEnglish (US)
Pages (from-to)884-889
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number2
DOIs
StatePublished - Jan 22 2002

ASJC Scopus subject areas

  • General

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