The T cell antigen receptor (TCR) recognizes foreign antigens and translates such recognition events into intracellular signals that elicit a change in the cell from a dormant to an activated state. Much of this signaling process can be attributed to a multisubunit complex of proteins that associates directly with the TCR. This complex has been designated CD3 (cluster of differentiation 3). It is composed of five invariant polypeptide chains that associate to form three dimers: a heterodimer of g and e chains (CD3-g and CD3-e), a heterodimer of d and e chains (CD3-d and CD3-e) and a homodimer of two z chains (CD3-z) or a heterodimer of z and h chains (CD3-z and CD3-h). CD3-z and CD3-h are encoded by the same gene, but differ in their carboxyl-terminal ends due to an alternative splicing event. CD3-g, CD3-e and CD3-d each contain a single copy of a conserved immunoreceptor tyrosine-based activation motif (ITAM). In contrast, CD3-z contains three consecutive copies of the same motif. Phosphorylated ITAMs act as docking sites for protein kinases such as ZAP-70 and Syk and are also capable of regulating their kinase activity. The crystal structure of the ZAP-70 SH2 domains bound to CD3-z ITAMs has been solved.