title: Molecular characterization of the OspA(161-175) T cell epitope associated with treatment-resistant Lyme arthritis: differences among the three pathogenic species of Borrelia burgdorferi sensu lato.
abstract: Treatment-resistant Lyme arthritis, which may result from infection-induced autoimmunity, is associated with reactivity to a T cell epitope of outer-surface protein A (OspA(161-175)) of Borrelia burgdorferi sensu stricto (Bb). This syndrome has been noted primarily in the United States where only Bb is present, and rarely in Europe where Borrelia garinii (Bg) and Borrelia afzelii (Ba) predominate. To gain a better understanding of this epitope, we identified its species-specific polymorphisms, determined their immunogenicity, and characterized the contribution of individual amino acids. Based on published sequences the Bb peptide differed from the Ba peptide in six of the nine core residues (amino acids 165-173), whereas the Bg peptide usually differed in three of the nine residues. Lymphocytes from seven patients with treatment-resistant Lyme arthritis proliferated in response to the Bb peptide, but not to the Ba or Bg peptide. Substitution analysis showed that valine166 and threonine172 were critical for the immunogenicity of the Bb peptide. Thus, consistent with the geographic distribution of the illness, the European causative agents of Lyme borreliosis usually lack the putative pathogenic OspA epitope. These observations are consistent with the hypothesis that T cell recognition of this epitope is important in the induction of autoimmunity in treatment-resistant Lyme arthritis.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. edrouin@partners.org
authors.forename: Elise E
authors.initials: EE
authors.lastname: Drouin
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Glickstein
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D001170:Arthritis, Infectious / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D001428:Bacterial Vaccines; D025065:Borrelia burgdorferi / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D018984:Epitopes, T-Lymphocyte / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D008193:Lyme Disease / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008074:Lipoproteins; C072045:OspA protein; D010446:Peptide Fragments