CHANGES AT PEPTIDE RESIDUES BURIED IN THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-I BINDING CLEFT INFLUENCE T-CELL RECOGNITION - A POSSIBLE ROLE FOR INDIRECT CONFORMATIONAL ALTERATIONS IN THE MHC CLASS-I OR BOUND PEPTIDE IN DETERMINING T-CELL RECOGNITION

Abstract

Recent crystallographic studies on two peptide complexes with the mouse Kb molecule have shown that peptide binding appears to alter the conformation of the class I alpha-helical regions that flank the antigen binding cleft. Given that this study also showed that much of the foreign peptide is buried within the class I binding cleft with only a small portion accessible for direct interaction with the components of the T cell receptor, this finding suggests that at least some component of T cell specificity may arise as a consequence of peptide-induced conformational changes in the class I structure. To assess this possibility, we have made systematic substitutions at residues within the Kb-r..