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

Abstract

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.

• Authors: Elise E Drouin, Lisa Glickstein, William W Kwok, Gerald T Nepom, Allen C Steere
• Journal: Molecular immunology (Mol Immunol) Vol. 45 Issue 8 Pg. 2323-32 (Apr 2008) ISSN: 0161-5890 [Print] England
• PMID: 18191206 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, microbiology)
• Peptides (immunology)
• Sequence Homology, Amino Acid
• T-Lymphocytes (microbiology)