Temporally regulated assembly of a dynamic signaling complex associated with the activated TCR

TCR triggering promotes multiple tyrosine kinase-dependent interactions involving proteins with one or more protein binding modules. Reported interactions mostly exceed the binding potential of these proteins. A solution to this paradox is the temporally regulated recruitment of alternative ligands. We have tested this hypothesis by analyzing the time course of protein/protein interactions triggered by TCR engagement. We show that a short-lived and dynamic multimolecular complex is assembled on tyrosine-phosphorylated CD3zeta. Specific components of this complex are recruited and shed in a temporal sequence distinct for each of the proteins analyzed. The temporally regulated assembly of a higher order structure at the activated TCR is likely to be crucial in achieving both signal longevity and signal specificity.