T cell receptor signaling kinase dynamics after APC activation. Co-activating CD28 becomes deficient via immunosenescence thus corrupting T cell efficiency in the elderly. 26.10.2021 DJGPhD.

The Src-family kinase Lck regulates T-cell development, activation, proliferation, and immune synapse dynamics. These are the initiation phases of TCR  signaling. Upon antigen presentation via the APC- TCR immune synapse, Lck phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR-associated CD3 membrane protein domains.

 Phosphorylated ITAMs function as a molecular platform  for  tandem SH2 domains located on  the tyrosine kinase Zap-70, initially activated by Lck. 

Lck kinase activity is regulated at  two canonical  phosphorylation sites Tyr394 and Tyr505, wherein auto-transphosphorylation of Tyr394 in the kinase domain erupts a relaxed/active conformation but phosphorylation of Tyr505, located at the C-terminus, by the tyrosine kinase Csk results in an inactive enzyme.

References

Longev Healthspan. 2012; 1: 6

SCIENCE ADVANCES•19 Jun 2019•Vol 5, Issue 6