Figure 1.

TCR signaling modules. (A) TCR signaling scheme. The first module (1) is responsible for transformation of the interaction of TCR with antigenic peptide associated with MHC class molecule into an intracellular signal. The second module amplifies this signal (2) and further diversifies it (-a–e). Both TCR-CD3 complex (δ, ε, γ, ζ subunits) and CD28 receptor are initially tyrosine-phosphorylated by SFK. (B) TCR signaling inhibiting proteins (iICPs). Numerous negative feedback proteins of TCR signaling were recently discovered. Here, these potential iICPs are classified in order of their clinical approval stage. The color of each iICP backing corresponds to the TCR signaling module where this protein represses the TCR signal. iICP, intracellular immune checkpoint; MHC, major histocompatibility complex; SFK, Src-family protein tyrosine kinases; TCR, T-cell receptor.