Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction

Linker for activation of T cells (LAT) is an adaptor protein whose tyrosine phosphorylation is critical for transduction of the T cell receptor (TCR) signal. LAT phosphorylation is accomplished by the protein tyrosine kinase ZAP-70, but it is not at all clear how LAT (which is not associated with th e TCR) encounters ZAP-70 (which is bound to the TCR). Here we show that LAT associates with surface CD4 and CD8 coreceptors and that its association i s promoted by the same coreceptor cysteine motif that mediates Lck binding. In Get, LAT competes with Lck for binding to individual coreceptor molecul es but differs from Lck in its preferential association with CD8 rather tha n CD4 ill CD4(+)CD8(+) thymocytes. Importantly, as a consequence of LAT ass ociation with surface coreceptors, coengagement of the TCR with surface cor eceptors induces LAT phosphorylation and the specific recruitment of downst ream signaling mediators to coreceptor-associated LAT molecules. These resu lts point to a new function for CD-F and CD8 coreceptors in TCR signal tran sduction, namely to promote LAT phosphorylation by ZAP-70 by recruiting LAT to major histocompatibility complex-engaged TCR complexes.