Determination of the Agretopic Residues of a Peptide Co-Restricted to Different Class II Isotypes, I-A^u and I-E^u, and Its Application for Preparation of a Synthetic Peptide Vaccine against Influenza Virus A/Aichi/2/68

Abstract

We have defined that residues 46 and 54 on a synthetic peptide composed of residues 43-58 of pigeon cytochrome c (p43-58) work as agretopes (sites bound to an MHC molecule) in I-A^b mice. Substitution of amino acid residues on these positions altered the peptide to bind with the other MHC molecules. Furthermore, by substituting the agretopic residues with a variety of amino acids, we could determine the class II binding motif for each MHC molecule. In the present study, immunogenicity of a peptide, 46R50V54A, carrying valine (V) at epitopic (site bound to TCR) position 50, arginine (R) and alanine (A) at agretopic positions 46 and 54 of the p43-58, respectively has been analyzed in B10.PL (H-2^u) mice. We found that this peptide bound to two different class II isotypes, I-A^u and I-E^u. Arginine at position 46 or alanine at position 54 of the 46R50V54A was shown to be critical for binding to I-A^u or I-E^u, respectively. Further, on the basis of this class II binding motif we could prepare potent peptide vaccines against influenza A/Aichi/2/68 virus in B10. PL mice.