QUANTITATION OF PEPTIDE ANCHOR RESIDUE CONTRIBUTIONS TO CLASS-I MAJORHISTOCOMPATIBILITY COMPLEX MOLECULE-BINDING

Class I major histocompatibility complex molecules play an important r ole in cellular immunity by presenting antigenic peptides to cytotoxic T cells. Deep polymorphic pockets in the peptide-binding groove of cl ass I major histocompatibility complex molecules provide structural co mplementarity for peptide ''anchor'' side chains. However, the minimum requirements of a peptide for high-affinity binding and the contribut ion of anchor side chains to binding have not been determined yet. To address these issues, we have compared the affinities of various octap eptides for purified, soluble H-2K(b) molecules. The results revealed that at least 2 anchor residues are necessary for high-affinity bindin g, and that high-affinity binding occurs only when anchor side chains are optimally packed within the groove. The estimated free energy cont ribution of two anchor side chains to binding is unexpectedly large an d comparable with that of peptide backbone, suggesting a crucial role of anchor residues in high-affinity, and hence specific, binding to cl ass I molecules.