High structural side chain specificity required at the second position of immunogenic peptides to obtain stable MHC/peptide complexes

Peptides binding to HLA-A11 contain a hydrophobic or a small polar amino acid at position 2 and a lysine at the carboxy terminus, Synthetic peptides carrying natural and unnatural amino acids in position 2 were used to determine the requirements for formation of stable HLA-A11/peptide complexes. By kinetic analysis we demonstrate that a stereospecific interaction between the side chain residue in position 2 and a subsite of pocket B is required to obtain stable HLA/peptide complexes, This specific interaction is mediated by a methyl group or by an ethyl group bound to the asymmetric C-beta atom with the correct configuration, Experiments performed with different peptide sequences suggest that the presence of adequate anchor residues may be sufficient to produce stable HLA/peptide complexes. (C) 1998 Federation of European Biochemical Societies.