Architectural Changes in the TCR:CD3 Complex Induced by MHC:Peptide Ligation

A hallmark of T cell activation is the ligation-induced down-modulation of the TCR:CD3 complex. However, little is known about the molecular events that drive this process. The CD3 ζ-chain has been shown to play a unique role in regulating the assembly, transport, and cell surface expression of the TCR:CD3 complex. In this study we have investigated the relationship between CD3ζ and the TCRαβCDR3εδγ complex after ligation by MHC:peptide complexes. Our results show that there is a significant increase in free surface CD3ζ, which is not associated with the TCR:CD3 complex, after T cell stimulation. This may reflect dissociation of CD3ζ from the TCRαβCD3εδγ complex or transport of intracellular CD3ζ directly to the cell surface. We also show that MHC:peptide ligation also results in exposure of the TCR-associated CD3ζ NH₂ terminus, which is ordinarily buried in the complex. These observations appears to be dependent on Src family protein tyrosine kinases, which are known to be critical for efficient T cell activation. These data suggest a mechanism by which ligated TCR may be differentiated from unligated TCR and selectively down-modulated.