Protein tyrosine kinase p59fyn is associated with the T cell receptor-CD3 complex in functional human lymphocytes.

The binding of antigen to the multicomponent T cell antigen receptor (TcR)-CD3 complex leads to the activation of several signal transduction pathways which result in T lymphocyte proliferation and lymphokine secretion by molecular mechanisms and catalytic molecules as yet poorly defined. One of the earliest events that follows the triggering of the antigen-specific TcR-CD3 complex is a rapid tyrosine phosphorylation of several intracellular substrates, suggesting stimulation of at least one protein tyrosine kinase (PTK). Since none of the seven TcR-CD3 subunits exhibits a recognizable kinase domain, it seems likely that the receptor complex is associated with an intracellular PTK. p59fyn and the T lymphocyte-specific p56lck are two intracellular, non-receptor, cell membrane-associated PTK of the src family expressed in T lymphocytes. Here, we show by double immunofluorescence microscopy a specific co-distribution of p59fyn, but not p56lck, with antibody-induced TcR or CD3 caps in intact human T lymphocytes. These findings provide direct evidence for a significant association of p59fyn with the TcR-CD3 complex under physiologically relevant conditions in functional T lymphocytes. They suggest that p59fyn is a crucial component of the TcR signal transduction machinery and that one of the earliest consequences of antigen recognition by the TcR is p59fyn-mediated phosphorylation of intracellular substrates on tyrosine residues.