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

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 beta2-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 (Arg2), 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.

• Authors: Y Sobao, N Tsuchiya, M Takiguchi, K Tokunaga
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 42 Issue 1 Pg. 175-81 (Jan 1999) ISSN: 0004-3591 [Print] United States
• PMID: 9920028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-B Antigens
• HLA-B27 Antigen
• HLA-B39 Antigen
• Peptides

Topics

• Amino Acid Sequence
• Antibody Specificity
• Binding Sites, Antibody
• Cross Reactions
• Genes, Overlapping
• HLA-B Antigens (immunology)
• HLA-B27 Antigen (immunology)
• HLA-B39 Antigen
• Humans
• Joint Diseases (etiology)
• Peptides (genetics, immunology, metabolism)
• Protein Binding (genetics)
• Spinal Diseases (etiology)
• Transfection