In vivo recognition of functionally empty class I molecules by a T cell receptor

The recognition of peptide in the binding site of MHC molecules provides the basis for current understanding of T cell recognition during immune surveilance, repertoire development, and tolerance. The contribution of MHC structural diversity, a central feature of these molecules, is appreciated in the context of amino acid differences that influence the peptide binding site and, presumably, the array of peptides displayed at the cell surface. However, activated CTL expressing the 2C TCR are able to specifically recognize the allogeneic class I molecules, Kbm3, and Ld, in the absence of their bound peptides on the surface of TAP deficient cells. Lysis of T2 cells expressing these molecules is inhibited by the exogenous addition of irrelevant peptide, demonstrating that the peptide binding site of the targeted class I molecules are not occupied by high affinity peptide. The 2C T cell can recognize peptide-deficient Kbm3 class I molecules in vivo as well, positively selecting class I restricted 2C transgenic T cells into the CD8 lineage in a TAP deficient background. These findings indicate that structural changes in the class I heavy chain can have a direct influence on T cell recognition and suggests that the nature of the TCR interaction with the class I heavy chain may influence the array of T cell receptors selected during development for the adult repertoire.