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

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-la, 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-1 alpha (L), we used OspA-specific T cell hybrids from DR4 transgenic mice, as well as cloned human cells specific for OspA(165-184) the immunodominant epitope, from five DRB1*0401(+) patients, using OspA-MHC class II tetramers. Although OSPA(165-184) stimulated nearly all OspA-specific human T cell clones tested to proliferate and secrete IFN-gamma and IL-13, LFA-1 alpha (L326-345) stimulated similar to 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-1 alpha (L326-345) behaves as a partial agonist, perhaps playing a role in perpetuating symptoms of arthritis.