Overlapping peptide-binding specificities of HLA-B27 and B39 - Evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies

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 beta(2)-microglobulin and HLA class I heavy chain genes. Results. Four of the 10 HLA-B27 binding peptides significantly bound to HLA-B*3901, AU 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.