Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis.

Antibiotic-refractory Lyme arthritis, which may result from infection-induced autoimmunity, is associated with HLA-DR molecules that bind an epitope of Borrelia burgdorferi (Bb) outer-surface protein A (OspA165–173) and with T cell reactivity with this epitope. One potential mechanism to explain these associations is molecular mimicry between OspA165–173 and a self-peptide. Here, we searched the published human genome for peptides with sequence homology with OspA165–173. The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP276–288, which had identity at eight of the nine core amino acid residues, and T-span758–70, which had identity at six residues. MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not. However, neither peptide bound all of the HLA-DR molecules associated with antibiotic-refractory Lyme arthritis. Among 11 patients, 9 had T cell reactivity with OspA161–170, 6 had responses to MAWD-BP276–288, and 3 had reactivity with T-span758–70, but reactivity with the self-peptides was lower than that induced by the spirochetal epitope. Thus, there remains an association between OspA165–173 and antibiotic-refractory Lyme arthritis, and infection-induced autoimmunity is an attractive hypothesis to explain this outcome. However, molecular mimicry due to sequence homology between OspA165–173 and a human peptide seems unlikely to be the critical mechanism.