I-Ad-binding peptides derived from unrelated protein antigens share a common structural motif
Sette, A.; Buus, S.; Colon, S.; Miles, C.; Grey, H.M.
Journal of Immunology 141(1): 45-48
1988
ISSN/ISBN: 0022-1767 PMID: 2837512 Document Number: 324346
Purified Ia molecules can specifically bind many unrelated peptide Ag, and such binding appears to be a necessary, albeit not sufficient, prerequisite for the immunogenicity of the proteins from which such peptides are derived. We have recently analyzed the affect of single amino acid substitutions on the I-Ad binding of the immunogenic peptide OVA 323-339. The results obtained demonstrated the very permissive nature of Ag-Ia interaction. We also showed that unrelated peptides that are good I-Ad binders share a common structural motif and speculated that recognition of such motifs could represent a mechanism to achieve a very permissive type of interaction that yet retained some degree of specificity. In the present set of experiments we analyzed the I-Ad binding pattern of a series of overlapping peptides derived from sperm whale myoglobin (residues 102-125) and influenza hemagglutinin (residues 121-146) to determine whether the peptide regions predicted on the basis of structural similarity to be involved in I-Ad binding were in fact involved. In both cases, the I-Ad-interacting determinants were found to contain the sequence motif postulated to be important for I-Ad binding. These data support the hypothesis that I-Ad molecules recognize a large library of Ag by virtue of common structural motifs present in peptides derived from phylogenetically unrelated proteins.