HIGH STRUCTURAL SIDE-CHAIN SPECIFICITY REQUIRED AT THE 2ND POSITION OF IMMUNOGENIC PEPTIDES TO OBTAIN STABLE MHC PEPTIDE COMPLEXES/

Peptides binding to HLA-A11 contain a hydrophobic or a small polar ami no 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/pe ptide complexes. By kinetic analysis we demonstrate that a stereospeci fic interaction between the side chain residue in position 2 and a sub site of pocket B is required to obtain stable HLA/peptide complexes, T his specific interaction is mediated by a methyl group or by an ethyl group bound to the asymmetric C-beta atom with the correct configurati on, Experiments performed with different peptide sequences suggest tha t the presence of adequate anchor residues may be sufficient to produc e stable HLA/peptide complexes. (C) 1998 Federation of European Bioche mical Societies.