A REQUIREMENT FOR THE RHO-FAMILY GTP EXCHANGE FACTOR VAV IN POSITIVE AND NEGATIVE SELECTION OF THYMOCYTES

The T cell repertoire is shaped by positive and negative selection of thymocytes that express low levels of T cell receptor (TCR) and both C D4 and CD8. TCR-mediated signals that determine these selection proces ses 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 tha t mice lacking Vav are viable and display a profound defect in the pos itive selection of both class I-and class Ii-restricted T cells. In co ntrast, Vav is not essential for negative selection, though in its abs ence negative selection is much less effective. Vav may influence the efficiency of TCR-induced selection events by regulating the intracell ular calcium flux of thymocytes.