Signal transduction by the T cell antigen receptor.

Overview

The T cell antigen receptor (TCR) must recognize antigen, and translate this recognition event into intracellular signal transduction events. Two signal transduction events are regulated by the TCR: the activation of a protein tyrosine kinase (PTK) and phospholipase C (PLC). Recent studies suggest that the TCR-activated PTK regulates PLC activation by the phosphorylation of tyrosine residues of PLC gamma 1. The complex structure of the TCR is now being related to its signal transduction function. Studies with chimeric receptors reveal that the antigen binding Ti heterodimer communicates with the subunits involved with signal transduction, the CD3 chains and zeta dimers, through the carboxy-terminal regions of the Ti chains that surround and include the transmembrane domains. Other chimeras have helped demonstrate that the zeta chain family of dimers function to couple the TCR to intracellular signal transduction mechanisms. The signal transduction function of the TCR can be regulated in a number of ways and by other T cell surface molecules. The plasma membrane tyrosine phosphatase CD45, plays a critical role to specifically regulate TCR-mediated activation of PTK's and PLC. Thus, an understanding of the complex structure of the TCR and the intricacies of its signal transduction function is rapidly emerging.