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.
Steere, Allen C. 1; Falk, Ben 4; Drouin, Elise E. 1; Baxter-Lowe, Lee Ann 2; Hammer, Juergen 3; Nepom, Gerald T. 4
[Article] Arthritis & Rheumatism. 48(2):534-540, February 2003.

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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 OspA163-175 and hLFA-1[alpha]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 OspA163-175 well, but hLFA-1[alpha]L330-342 only weakly; the DRB1*0801 or *1101 molecule bound both peptides weakly, if at all. The magnitude of OspA163-175 binding correlated well with the frequencies of the DRB1 alleles in patients with treatment-resistant arthritis, but the binding of hLFA-1[alpha]L330-342 showed only an association with the DRB*04 alleles.

Conclusion. These correlations support the hypothesis that OspA163-175 is the critical epitope in triggering antibiotic treatment-resistant Lyme arthritis. However, the inability of the DRB*0101 molecule to bind hLFA-1[alpha]L330-342 suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101-positive patients.

(C) 2003, American College of Rheumatology