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

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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 OspA163–175 and hLFA‐1αL330–342 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‐1αL330–342 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‐1αL330–342 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‐1αL330–342 suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101‐positive patients.