The binding of CD4/CD8 to non-polymorphic regions of MHC brings Lck in to proximity with TCR subunits phosphorylation. Lck is further phosphorylated to promote the active conformation and to increase their catalytic activity. The C-term domain contain a regulatory activation loop, which is the site of activating Tyr 394 phosphorylation. This tyrosine is auto-phosphorylated to attain an active conformation on TCR stimulation. Now Lck through its kinase activity phosphorylates the ITAMs in TCR zeta and CD3 members.
Palacios, EH, Weiss, A
protein tyrosine kinase activity of Antigen-bearing MHC Class II : TCR complex:CD4:Lck [plasma membrane]
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