Schematic representation of T-cell receptor signal transduction. CD4-associated Lck is reciprocally regulated by CD45 and Csk/PTPN22 and in turn phosphorylates CD3 chain immunoreceptor tyrosine-based activating motifs (ITAMs) and ZAP-70. ZAP-70 phosphorylates additional downstream effectors, including the adaptors Slp-76 and Lat. Yellow bands represent CD3 chain ITAM domains. Phosphotyrosines are not depicted on all CD3 chain ITAMs. MAPK, mitogen-activated protein kinase; PLCγ1, phospholipase C γ1; TCR, T-cell antigen receptor.