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

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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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
Externally publishedYes

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T-Lymphocytes
Thymocytes
src Homology Domains
Binding Sites
Extracellular Signal-Regulated MAP Kinases
T-Cell Antigen Receptor
Transgenes
Protein Kinases
Antibody Formation
Ligation
Hypersensitivity
Spleen
Immunoglobulin G
Cell Proliferation
Calcium
Skin

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Differential role of SLP-76 domains in T cell development and function. / Kumar, Lalit; Pivniouk, Vadim I; De La Fuente, Miguel A.; Laouini, Dhafer; Geha, Raif S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 2, 22.01.2002, p. 884-889.

Research output: Contribution to journalArticle

Kumar, Lalit ; Pivniouk, Vadim I ; De La Fuente, Miguel A. ; Laouini, Dhafer ; Geha, Raif S. / Differential role of SLP-76 domains in T cell development and function. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 2. pp. 884-889.
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