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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 for 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.

Type

Journal article

Journal

Immunity

Publication Date

10/1997

Volume

7

Pages

451 - 460

Keywords

Animals, Calcium, Cell Cycle Proteins, Clonal Deletion, Guanine Nucleotide Exchange Factors, Mice, Mice, Inbred BALB C, Mice, Knockout, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocyte Subsets, Thymus Gland