Role of the T cell receptor alpha chain in stabilizing TCR-superantigen-MHC class II complexes

Superantigens (SAGs) activate T cells by simultaneously binding the VB doma in of the TCR and MHC class II molecules on antigen-presenting cells. The p referential expression of certain Va regions among SAG-reactive T cells has suggested that the TCR alpha chain may modulate the level of activation th rough an interaction with MHC. We demonstrate that the TCR alpha chain is r equired for maximum stabilization of the TCR-SAG-MHC complex and that the a lpha chain increases the half-life of the complex to match those of TCR-pep tide/MHC complexes. The site on the TCR alpha chain responsible for these e ffects is CDR2. Thus, the overall stability of the TCR-SAG-MHC complex is d etermined by the combination of three distinct interactions: TCR-SAG, SAG-M HC, and MHC-TCR.