B2707 differs in peptide specificity from B2705 and B2704 as much as from HLA‐B27 subtypes not associated to spondyloarthritis

HLA‐B*2707 is associated with ankylosing spondylitis in most populations. Like the non‐associated allotypes B*2706 and B*2709, it lacks Asp116 and shows preference for peptides with nonpolar C‐terminal residues. The relationships between the peptide specificity of B*2707 and those of the disease‐associated B*2705 and the non‐associated subtypes were analyzed by determining the overlap between the corresponding peptide repertoires, the sequence of shared and differential ligands, and by comparing allospecific T cell epitopes with peptide sharing. The B*2707‐bound repertoire was as different from that of B*2705 as from those of B*2706, B*2709, or the two latter subtypes from each other. Differences between B*2707 and B*2705 were based on their C‐terminal residue specificity and a subtle modulation at other positions. Differential usage of secondary anchor residues explained the disparity between the B*2707‐, B*2706‐, and B*2709‐bound repertoires. Similar differences in residue usage were found between B*2707 and both B*2704 and B*2706, as expected from the high peptide overlap between the two latter subtypes. T cell cross‐reaction paralleled peptide sharing, suggesting that many shared ligands conserve their alloantigenic features on distinct subtypes. Our results indicate that association of HLA‐B27 subtypes with ankylosing spondylitis does not correlate with higher peptide sharing among disease‐associated subtypes or with obvious peptide motifs.