DIFFERENCES IN MHC CLASS-I SELF-PEPTIDE REPERTOIRES AMONG HLA-A2 SUBTYPES

To investigate how single amino acid substitutions in MHC class I mole cules affect differences in peptide repertoires, we eluted and sequenc ed the naturally processed peptides from three HLA-A2 subtypes (HLA-A 0204, -A0206, and -A*0207) that differ by a single amino acid residue substitution each with HLA-A0201 at the floor of the binding groove. Allele-specific peptide motifs for each HLA-A2 subtype substantially differed from that of HLA-A0201 in the dominant anchor residues. The relative signal intensities for 18 self peptides, determined by mass s pectrometry, precisely reflected these peptide motifs. Some overlappin g peptides were isolated from both HLA-A0201 and a single HLA-A2 vari ant, but no peptide was ubiquitously found across all variants. To rat ionalize 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-A0201. According to ou r models, the differences in peptide motifs could be explained by subs tituted-residue-driven conformational changes for each MHC-peptide com plex. These results demonstrate the fine differences between HLA-A2 su btype self peptide repertoires and contribute to the prediction of ant igenic peptides.