B*2707 differs in peptide specificity from B*2705 and B*2704 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.
Gómez
Patricia
P
Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Facultad de Ciencias, Universidad Autónoma, Madrid, Spain.
Montserrat
Verónica
V
Marcilla
Miguel
M
Paradela
Alberto
A
de Castro
José A López
JA
D020816:Amino Acid Motifs; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism*; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism*; D015796:HLA-B27 Antigen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D025241:Spondylarthritis / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C510610:HLA-B*27:04 antigen; C464936:HLA-B*27:05 antigen; C513088:HLA-B*27:07 antigen; D015796:HLA-B27 Antigen; D010455:Peptides