The Src-like adaptor protein downregulates the T cell receptor on CD4(+)CD8(+) thymocytes and regulates positive selection

In this report, we show that the Src-like adaptor protein (SLAP) plays an i mportant role in thymocyte development. SLAP expression is developmentally regulated; it is low in CD4(-)CD8(-) thymocytes, it peaks in the CD4(+)CD8( +) subset, and it decreases to low levels in more mature cells. Disruption of the SLAP gene leads to a marked upregulation of TCR and CD5 expression a t the CD4(+)CD8(+) stage. The absence of SLAP was also developmentally sign ificant because it enhanced positive selection in mice expressing the DO11. 10 transgenic T cell receptor. Moreover, SLAP deletion at least partially r escued the development of ZAP-70-deficient thymocytes. These results demons trate that SLAP participates in a novel mechanism of TCR downregulation at the CD4(+)CD8(+) stage and regulates positive selection.