Binding of Outer Surface Protein A and Human Lymphocyte Function-Associated Antigen 1 Peptides to HLA-DR Molecules Associated With Antibiotic Treatment-Resistant Lyme Arthritis

Arthritis Rheum. 2003 Feb;48(2):534-40. doi: 10.1002/art.10772.

Abstract

Objective: To assess the binding of outer surface protein A (OspA) and human lymphocyte function-associated antigen 1 (hLFA-1) peptides to 5 major histocompatibility complex (MHC) molecules.

Methods: Peptide binding to the MHC molecules was determined by in vitro binding assays, and binding was correlated with the frequencies of the 5 MHC molecules in patients with treatment-resistant Lyme arthritis.

Results: The HLA-DRB1*0401 molecule bound both OspA(163-175) and hLFA-1alpha(L330-342) well. Although the magnitude of the binding was less, the DRB1*0404 molecule also showed binding of both peptides. The DRB1*0101 molecule bound OspA(163-175) well, but hLFA-1alpha(L330-342) only weakly; the DRB1*0801 or *1101 molecule bound both peptides weakly, if at all. The magnitude of OspA(163-175) binding correlated well with the frequencies of the DRB1 alleles in patients with treatment-resistant arthritis, but the binding of hLFA-1alpha(L330-342) showed only an association with the DRB*04 alleles.

Conclusion: These correlations support the hypothesis that OspA(163-175) is the critical epitope in triggering antibiotic treatment-resistant Lyme arthritis. However, the inability of the DRB*0101 molecule to bind hLFA-1alpha(L330-342) suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101-positive patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Surface / metabolism*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Vaccines
  • Binding, Competitive
  • Drug Resistance, Bacterial
  • Gene Frequency
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / metabolism*
  • Humans
  • In Vitro Techniques
  • Lipoproteins*
  • Lyme Disease / drug therapy*
  • Lyme Disease / genetics
  • Lyme Disease / immunology*
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Peptide Fragments / metabolism

Substances

  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • HLA-DR Antigens
  • Lipoproteins
  • Lymphocyte Function-Associated Antigen-1
  • OspA protein
  • Peptide Fragments