Figure 1.

Signalling is initiated by engagement of the TCR and costimulatory molecules, such as CD28. Phosphorylation of proximal signalling molecules TCR-ζ chain, ZAP-70 and adaptor molecules LAT and SLP-76 by protein tyrosine kinases coordinate the activation of second messenger cascades leading to cytoskeletal reorganization and transcriptional activation. The threshold for TCR activation is regulated by the type of costimulatory molecule expressed, CTLA-4 will downregulate TCR activation, and the regulation of the proximal src-family kinase, LCK. LCK homeostasis is controlled by the reciprocal action of CD45 and CSK. Protein tyrosine kinases are shown in blue, adaptor proteins are orange. Modified from Singer and Koretzky.²¹