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 α-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-restr..