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Antibiotic-refractory Lyme arthritis is believed to result from an infection-induced autoimmune response triggered by the spirochete Borrelia burgdorferi ( Bb ). Disease susceptibility is associated with the HLA alleles DRB1*0101, 0401, 0402, 0404, 0405 and DRB5*0101, and all these MHC molecules bind the Bb epitope OspA 163–175. However, not all patients have a proliferative response to this epitope. To identify other possible Bb epitopes involved in this disease process, the algorithm TEPITOPE was used to scan 17 immunogenic Bb proteins for potential T cell epitopes with a refractory arthritis-associated MHC binding profile, and the Bb proteome was searched for peptides with sequence homology to OspA 165–173 . Sixteen promising T epitopes were identified and their MHC binding profiles to 13 MHC molecules were verified using in vitro MHC/peptide binding assays. One peptide, BBK32 392–404 , had a strong refractory arthritis-associated MHC binding profile, and another GK 297–306 shared sequence homology to OspA 165–173 . However, patient cells did not proliferate in response to either peptide making it highly unlikely they were involved in a refractory course. A comparison of the in silico and in vitro results revealed that TEPITOPE correctly predicted 74% of the in vitro binding peptides, but it incorrectly predicted that 44% of the in vitro non binding peptides would bind. For a particular MHC molecule, concordance between the in silico and in vitro results varied anywhere between 33% and 100%. Therefore, while additional Bb epitopes may be involved in the development of antibiotic-refractory Lyme arthritis, recognition of OspA 163–175 remains the only known Bb epitope associated with this disease course. |
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