When T-cell receptors become clustered on binding MHC:peptide complexes on the surface of an antigen-presenting cell, activation of receptor-associated kinases such as Fyn leads to phosphorylation of the CD3γ, δ, and ε ITAMs as well as those on the ζ chain. The tyrosine kinase ZAP-70 binds to the phosphorylated ITAMs of the ζ chain, but is not activated until binding of the co-receptor to the MHC molecule on the antigen-presenting cell (here shown as CD4 binding to an MHC class II molecule) brings the kinase Lck into the complex. Lck then phosphorylates and activates ZAP-70.