Searching for borrelial T cell epitopes associated with antibiotic-refractory Lyme arthritis

Mol Immunol. 2008 Apr;45(8):2323-32. doi: 10.1016/j.molimm.2007.11.010. Epub 2008 Jan 11.


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 vitrononbinding 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / immunology
  • Borrelia burgdorferi / immunology*
  • Computational Biology
  • Computers
  • Drug Resistance, Microbial / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-DR Antigens / immunology
  • Humans
  • Lyme Disease / immunology*
  • Lyme Disease / microbiology*
  • Peptides / immunology
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / microbiology


  • Bacterial Proteins
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • Peptides