Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1αL Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells

  • Trollmo C
  • Meyer A
  • Steere A
  • et al.
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Abstract

Antibiotic treatment-resistant Lyme arthritis is a chronic inflammatory joint disease that follows infection with Borrelia burgdorferi (Bb). A marked Ab and T cell response to Bb outer surface protein A (OspA) often develops during prolonged episodes of arthritis. Furthermore, cross-reaction between the bacterial OspA and human LFA-1αL at the T cell level and the inability to detect Bb in the joint implicate an autoimmune mechanism. To analyze the nature of response to OspA and LFA-1αL, we used OspA-specific T cell hybrids from DR4 transgenic mice, as well as cloned human cells specific for OspA165–184, the immunodominant epitope, from five DRB1*0401+ patients, using OspA-MHC class II tetramers. Although OspA165–184 stimulated nearly all OspA-specific human T cell clones tested to proliferate and secrete IFN-γ and IL-13, LFA-1αL326–345 stimulated ∼10% of these clones to proliferate and a greater percentage to secrete IL-13. Assays with LFA- or OspA-DR4 monomers revealed that higher concentrations of LFA-DR4 were needed to stimulate dual-reactive T cell hybrids. Our analysis at the clonal level demonstrates that human LFA-1αL326–345 behaves as a partial agonist, perhaps playing a role in perpetuating symptoms of arthritis.

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APA

Trollmo, C., Meyer, A. L., Steere, A. C., Hafler, D. A., & Huber, B. T. (2001). Molecular Mimicry in Lyme Arthritis Demonstrated at the Single Cell Level: LFA-1αL Is a Partial Agonist for Outer Surface Protein A-Reactive T Cells. The Journal of Immunology, 166(8), 5286–5291. https://doi.org/10.4049/jimmunol.166.8.5286

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