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Mol Immunol. 2008 Jan;45(1):180-9. Epub 2007 Jun 6.

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

Author information

1
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. edrouin@partners.org

Abstract

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 (OspA(165-173)) and with T cell reactivity with this epitope. One potential mechanism to explain these associations is molecular mimicry between OspA(165-173) and a self-peptide. Here, we searched the published human genome for peptides with sequence homology with OspA(165-173). The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP(276-288), which had identity at eight of the nine core amino acid residues, and T-span7(58-70), 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 OspA(161-170), 6 had responses to MAWD-BP(276-288), and 3 had reactivity with T-span7(58-70), but reactivity with the self-peptides was lower than that induced by the spirochetal epitope. Thus, there remains an association between OspA(165-173) 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 OspA(165-173) and a human peptide seems unlikely to be the critical mechanism.

PMID:
17555819
PMCID:
PMC2075570
DOI:
10.1016/j.molimm.2007.04.017
[Indexed for MEDLINE]
Free PMC Article

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