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.
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.


CONCLUSIONS
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.
Steere
Allen C
AC
Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts, USA. asteere@partners.org
Falk
Ben
B
Drouin
Elise E
EE
Baxter-Lowe
Lee Ann
LA
Hammer
Juergen
J
Nepom
Gerald T
GT
D000954:Antigens, Surface / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001428:Bacterial Vaccines; D001667:Binding, Competitive; D024881:Drug Resistance, Bacterial; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins; D008193:Lyme Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D006684:HLA-DR Antigens; D008074:Lipoproteins; D016169:Lymphocyte Function-Associated Antigen-1; C072045:OspA protein; D010446:Peptide Fragments