When T cells encounter antigens via the T cell receptor (TCR), information about the quantity and quality of antigens is relayed to the intracellular signal transduction machinery. This activation process depends mainly on CD3 (Cluster of Differentiation 3), a multiunit protein complex that directly associates with the TCR. CD3 is composed of four polypeptides: ?, ?, ?, and ?. Each of these polypeptides contains at least one immunoreceptor tyrosine-based activation motif (ITAM). Engagement of the TCR complex with foreign antigens induces tyrosine phosphorylation in the ITAM motifs and phosphorylated ITAMs function as docking sites for signaling molecules such as ZAP-70 and the p85 subunit of PI-3 kinase. TCR ligation also induces a conformational change in CD3?, such that a proline region is exposed and then associates with the adaptor protein Nck.