A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes

Martin Turner, P. Joseph Mee, Alice E. Walters, Marian E. Quinn, Andrew L. Mellor, Rose Zamoyska, Victor L J Tybulewicz

Research output: Contribution to journalArticlepeer-review

254 Scopus citations

Abstract

The T cell repertoire is shaped by positive and negative selection of thymocytes that express low levels of T cell receptor (TCR) and both CD4 and CD8. TCR-mediated signals that determine these selection processes are only partly understood. Vav, a GDP-GTP exchange factor for Rho-family proteins, is tyrosine phosphorylated following TCR stimulation, suggesting that it may transduce TCR signals. We now demonstrate that mice lacking Vav are viable and display a profound defect in the positive selection of both class I- and class II-restricted T cells. In contrast, Vav is not essential far negative selection, though in its absence negative selection is much less effective. Vav may influence the efficiency of TCR-induced selection events by regulating the intracellular calcium flux of thymocytes.

Original languageEnglish (US)
Pages (from-to)451-460
Number of pages10
JournalImmunity
Volume7
Issue number4
DOIs
StatePublished - Oct 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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