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 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.
Turner
M
M
National Institute for Medical Research, The Ridgeway, London, United Kingdom.
Mee
P J
PJ
Walters
A E
AE
Quinn
M E
ME
Mellor
A L
AL
Zamoyska
R
R
Tybulewicz
V L
VL
D000818:Animals; D002118:Calcium / Q000502:physiology; D018797:Cell Cycle Proteins; D017637:Clonal Deletion; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496619:Vav1 protein, mouse; D002118:Calcium