Determination of the agretopic residues of a peptide co-restricted to different class II isotypes, I-Au and I-Eu, and its application for preparation of a synthetic peptide vaccine against influenza virus A/Aichi/2/68.
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-Ab 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-2u) mice. We found that this peptide bound to two different class II isotypes, I-Au and I-Eu. Arginine at position 46 or alanine at position 54 of the 46R50V54A was shown to be critical for binding to I-Au or I-Eu, 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.
Takami
K
K
Section of Pathology, Hokkaido University, Japan.
Ogasawara
K
K
Itoh
Y
Y
Kajino
K
K
Naruse
H
H
Onoé
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004285:Dogs; D000939:Epitopes / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D006825:Hybridomas; D007114:Immunization; D009980:Influenza A virus / Q000254:growth & development / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D010446:Peptide Fragments; D014614:Vaccines, Synthetic