To investigate how single amino acid substitutions in MHC class I molecules affect differences in peptide repertoires, we eluted and sequenced the naturally processed peptides from three HLA-A2 subtypes (HLA-A*0204, -A*0206 and -A*0207) which differ by a single amino acid residue substitution each with -A*0201 at the floor of the binding groove. Allele-specific peptide-motifs for each HLA-A2 subtype substantially differed from that of -A*0201 in the dominant anchor residues. The relative signal intensities for eighteen self peptides determined by mass spectrometry precisely reflected these peptide-motifs. To rationalize the differences in peptide-motifs, possible conformations of each allele were computer modeled by energy minimization calculations based on the reported crystal structure of HLA-A*0201. According to our models, the differences in peptide-motifs could be explained by substituted-residue-driven conformational changes for each MHC-peptide complex. These results demonstrate the fine differences among HLA-A2 subtype self peptide repertoires and contribute to the prediction of antigenic peptides.
|Number of pages||1|
|Journal||Japanese Journal of Human Genetics|
|Publication status||Published - Dec 1 1996|
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