I-Ad-binding peptides derived from unrelated protein antigens share a common structural motif.
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.
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Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Buus
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Colon
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Miles
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Grey
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000378:metabolism; D010047:Ovalbumin / Q000138:chemical synthesis / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000032:analysis; D013329:Structure-Activity Relationship
D000596:Amino Acids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D009211:Myoglobin; D010455:Peptides; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D010047:Ovalbumin