Closer Peptide Repertoire Similarity of HLA-B∗14:03 and HLA-B∗27:05 Sheds Light on Ankylosing Spondylitis Susceptibility.

ABSTRACT: The human major histocompatibility complex class I gene HLA-B∗27 is the main risk factor for ankylosing spondylitis (AS) through a mechanism that remains unknown. In African populations, where B∗27 is rare, the B∗14:03 allotype is strongly associated with AS, whereas B∗14:02, which differs at only one residue (L156R), is not associated. Using large-scale mass spectrometry-based peptide sequencing, we analyzed the peptidomes of HLA-B∗14:03, HLA-B∗14:02, and HLA-B∗27:05, obtaining more than 2000 ligands for each. Remarkably, we identified 1011 peptides shared by the AS-associated HLA-B∗27:05 and B∗14:03 alleles but not by the non-AS-associated B∗14:02 allele. Surprisingly, although B∗14:03 and B∗27:05 differ by 15 amino acids in their peptide-binding domain, they share a large portion of the

SUBMITTER: Cobos-Figueroa L 

PROVIDER: S-EPMC12284515 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature