The Peptide Repertoires of HLA-B27 Subtypes Differentially Associated to Spondyloarthropathy (B2704 and B2706) Differ by Specific Changes at Three Anchor Positions

• Published in: The Journal of biological chemistry 2002-05, Vol.277 (19), p.16744-16749
• Main Authors: Sesma, Laura, Montserrat, Verónica, Lamas, Jose Ramón, Marina, Anabel, Vázquez, Jesús, de Castro, José A. López
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - metabolism; Arginine - chemistry; Cell Line; Chromatography, High Pressure Liquid; Epitopes - chemistry; histocompatibility antigen HLA; HLA-B27 Antigen - chemistry; Humans; Immunoglobulin Allotypes - chemistry; Ligands; Mass Spectrometry; Molecular Sequence Data; Peptides - chemistry; Phenylalanine - chemistry; Polymorphism, Genetic; Protein Structure, Tertiary; Spondylitis - immunology; Spondylitis - metabolism; T-Lymphocytes - metabolism; T-Lymphocytes, Cytotoxic - metabolism; Tyrosine - chemistry
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M200371200

HLA-B*2704 is strongly associated with ankylosing spondylitis. B*2706, which differs from B*2704 by two amino acid changes, is not associated with this disease. A systematic comparison of the B*2704- and B*2706-bound peptide repertoires was carried out to elucidate their overlap and differential features and to correlate them with disease susceptibility. Both subtypes shared about 90% of their peptide repertoires, consisting of peptides with Arg2and C-terminal aliphatic or Phe residues. B*2706 polymorphism influenced specificity at three anchor positions: it favored basic residues at P3 and PΩ-2 and impaired binding of Tyr and Arg at PΩ. Thus, the main structural feature of peptides differentially bound to B*2704 was the presence of C-terminal Tyr or Arg, together with a strong preference for aliphatic/aromatic P3 residues. This is the only known feature of B*2704 and B*2706 that correlates to their differential association with spondyloarthropathy. The concomitant presence of basic P3 and PΩ-2 residues was observed only among peptides differentially bound to B*2706, suggesting that it impairs binding to B*2704. Similarity between peptide overlap and the degree of cross-reaction with alloreactive T lymphocytes suggested that the majority of shared ligands maintain unaltered antigenic features in the context of both subtypes.