Abstract
The earliest molecular events in T cell recognition have not yet been fully described, and the initial T cell receptor (TCR) triggering mechanism remains a subject of controversy. Here, using TIRF/FRET microscopy, we observe a two-stage interaction between TCR, CD8, and MHCp. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ-CD8 interactions require CD8-MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR triggering event is induced by free Lck.
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