The activation of T lymphocytes by antigens is mediated by the T cell receptor (TCR), which is a multisubunit complex assembled from at least six different genes . The TCR subunits include the Ti a and b chains, the CD3 g , d and e chains and a z -containing homodimer or heterodimer . The protein tyrosine kinase ZAP-70 binds to the phosphorylated immunoreceptor tyrosine-base activation motifs (ITAMs) of the TCR z chain through two src-homology (SH2) domains . This binding results in the phosphorylation of ZAP-70 on multiple tyrosine residues, including Tyr292 and Tyr319 . ZAP-70 is autophosphorylated on Tyr292, which is thought to negatively regulate ZAP-70 function in lymphocytes . Alternatively, ZAP-70 is positively regulated by phosphorylation on Tyr319, which mediates the SH2-dependent interaction between Lck and ZAP-70 .