Open AccessOverlapping peptide‐binding specificities of HLA–B27 and B39: Evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies
Author(s) -
Sobao Yuji,
Tsuchiya Naoyuki,
Takiguchi Masafumi,
Tokunaga Katsushi
Publication year - 1999
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199901)42:1<175::aid-anr21>3.0.co;2-7
Subject(s) - peptide , spondylarthropathies , amino acid , biology , pathogenesis , peptide sequence , human leukocyte antigen , n terminus , biochemistry , chemistry , antigen , gene , immunology , arthritis
Abstract Objective Previous studies indicated the increase of HLA–B39 among HLA–B27 negative patients with spondylarthropathies (SpA). This study was performed to examine whether the natural ligands of HLA–B27 are capable of binding to HLA–B39. Methods Peptides were synthesized according to the sequences of known natural ligands of HLA–B27 or B39 and were tested for their binding to HLA–B*3901 and B*2705 by quantitative peptide binding assay, using a TAP‐deficient RMA‐S cell line transfected with human β 2 ‐microglobulin and HLA class I heavy chain genes. Results Four of the 10 HLA–B27 binding peptides significantly bound to HLA–B*3901. All 4 peptides had hydrophobic/aromatic amino acids (Leu or Phe) at the C‐terminus. In contrast, peptides with basic residues (Lys, Arg) or Tyr at the C‐terminus did not bind to B*3901. In parallel experiments, 1 of the 2 natural ligands of HLA–B*3901 was found to bind to B*2705. Conclusion A subset of natural HLA–B27 ligands was capable of binding to B*3901. In addition to Arg at position 2 (Arg 2 ), hydrophobic/aromatic C‐terminal residues, such as Leu or Phe, seemed to be crucial for the cross‐specificity. These results suggested that HLA–B27 and B39 recognize overlapping peptide repertoires, supporting the hypothesis that the peptides presented by both of these class I antigens play a role in the pathogenesis of SpA.