Figure 1: Proximal TCR signaling
Following TCR engagement protein tyrosine kinases (PTKs) such as Lck, phosphorylate the tyrosine residues in the ITAMs in the cytoplasmic tails of CD3ζζ, which serve as docking sites for the Src homology 2 (SH2) domain containing tyrosine kinase ZAP-70. ZAP-70 phosphorylates adaptor proteins, including LAT and SLP-76, activating PI3-kinase pathway, Ras- MAPK pathways and Ca2+-mediated signalling. In the appropriate cytokine environment (red cytokines), CD4+ T cells differentiate into reversible TH1, TH2, TH9, TH17 and Treg cells and secrete a suite of characteristic cytokines (blue, bold cytokines).