Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Apr;64(4):1284–1289. doi: 10.1128/iai.64.4.1284-1289.1996

Dominant recognition of a Borrelia burgdorferi outer surface protein A peptide by T helper cells in patients with treatment-resistant Lyme arthritis.

T Kamradt 1, B Lengl-Janssen 1, A F Strauss 1, G Bansal 1, A C Steere 1
PMCID: PMC173916  PMID: 8606091

Abstract

In an earlier study, we found that T-cell lines (TCL) from five patients with treatment-resistant Lyme arthritis preferentially recognized Borrelia burgdorferi outer surface protein A (OspA), but TCL from four patients with treatment-responsive arthritis only rarely recognized this protein. Dominant T-cell recognition of an arthritogenic OspA epitope is one way in which the immune response against OspA might be involved in the pathogenesis of treatment-resistant Lyme arthritis. In an effort to test this hypothesis, we mapped the epitopes of 31 OspA-specific TCL and five T-cell clones derived from the synovial fluid or peripheral blood samples of three patients with treatment-resistant Lyme arthritis. Although each patient's TCL recognized a broad array of OspA peptides with different individual patterns, two regions of OspA were dominantly recognized. Each patient's TCL dominantly recognized a C-terminal epitope of OspA, ranging from amino acids (aa) 214 to 233 in one patient to 244 to 263 in another, and the TCL of all three patients dominantly recognized an epitope between aa 84 and 113. These dominant regions were confirmed by clonal analysis in one patient. Thus, the region of OspA between aa 84 and 113 was the dominant T-cell epitope shared by these three patients with treatment-resistant Lyme arthritis. If the T-cell response to OspA is involved in the pathogenesis of treatment-resistant Lyme arthritis, and epitope contained within aa 84 to 113 is a potentially arthritogenic epitope.

Full Text

The Full Text of this article is available as a PDF (232.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asch E. S., Bujak D. I., Weiss M., Peterson M. G., Weinstein A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol. 1994 Mar;21(3):454–461. [PubMed] [Google Scholar]
  2. Barbour A. G., Fish D. The biological and social phenomenon of Lyme disease. Science. 1993 Jun 11;260(5114):1610–1616. doi: 10.1126/science.8503006. [DOI] [PubMed] [Google Scholar]
  3. Bradley J. F., Johnson R. C., Goodman J. L. The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Intern Med. 1994 Mar 15;120(6):487–489. doi: 10.7326/0003-4819-120-6-199403150-00007. [DOI] [PubMed] [Google Scholar]
  4. Burmester G. R., Daser A., Kamradt T., Krause A., Mitchison N. A., Sieper J., Wolf N. Immunology of reactive arthritides. Annu Rev Immunol. 1995;13:229–250. doi: 10.1146/annurev.iy.13.040195.001305. [DOI] [PubMed] [Google Scholar]
  5. Chomarat P., Vannier E., Dechanet J., Rissoan M. C., Banchereau J., Dinarello C. A., Miossec P. Balance of IL-1 receptor antagonist/IL-1 beta in rheumatoid synovium and its regulation by IL-4 and IL-10. J Immunol. 1995 Feb 1;154(3):1432–1439. [PubMed] [Google Scholar]
  6. Fikrig E., Barthold S. W., Kantor F. S., Flavell R. A. Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science. 1990 Oct 26;250(4980):553–556. doi: 10.1126/science.2237407. [DOI] [PubMed] [Google Scholar]
  7. Fujinami R. S., Oldstone M. B. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science. 1985 Nov 29;230(4729):1043–1045. doi: 10.1126/science.2414848. [DOI] [PubMed] [Google Scholar]
  8. Gondolf K. B., Mihatsch M., Curschellas E., Dunn J. J., Batsford S. R. Induction of experimental allergic arthritis with outer surface proteins of Borrelia burgdorferi. Arthritis Rheum. 1994 Jul;37(7):1070–1077. doi: 10.1002/art.1780370713. [DOI] [PubMed] [Google Scholar]
  9. Hammers-Berggren S., Lebech A. M., Karlsson M., Andersson U., Hansen K., Stiernstedt G. Serological follow-up after treatment of Borrelia arthritis and acrodermatitis chronica atrophicans. Scand J Infect Dis. 1994;26(3):339–347. doi: 10.3109/00365549409011804. [DOI] [PubMed] [Google Scholar]
  10. Herzer P. Lyme arthritis in Europe: comparisons with reports from North America. Ann Rheum Dis. 1988 Sep;47(9):789–790. doi: 10.1136/ard.47.9.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Huppertz H. I., Karch H., Suschke H. J., Döring E., Ganser G., Thon A., Bentas W. Lyme arthritis in European children and adolescents. The Pediatric Rheumatology Collaborative Group. Arthritis Rheum. 1995 Mar;38(3):361–368. doi: 10.1002/art.1780380310. [DOI] [PubMed] [Google Scholar]
  12. Johnson B. J., Sviat S. L., Happ C. M., Dunn J. J., Frantz J. C., Mayer L. W., Piesman J. Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2. Vaccine. 1995 Aug;13(12):1086–1094. doi: 10.1016/0264-410x(95)00035-y. [DOI] [PubMed] [Google Scholar]
  13. Kalish R. A., Leong J. M., Steere A. C. Early and late antibody responses to full-length and truncated constructs of outer surface protein A of Borrelia burgdorferi in Lyme disease. Infect Immun. 1995 Jun;63(6):2228–2235. doi: 10.1128/iai.63.6.2228-2235.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kalish R. Lyme disease. Rheum Dis Clin North Am. 1993 May;19(2):399–426. [PubMed] [Google Scholar]
  15. Kamradt T., Krause A., Burmester G. R. A role for T cells in the pathogenesis of treatment-resistant Lyme arthritis. Mol Med. 1995 Jul;1(5):486–490. [PMC free article] [PubMed] [Google Scholar]
  16. Keller D., Koster F. T., Marks D. H., Hosbach P., Erdile L. F., Mays J. P. Safety and immunogenicity of a recombinant outer surface protein A Lyme vaccine. JAMA. 1994 Jun 8;271(22):1764–1768. [PubMed] [Google Scholar]
  17. Lahesmaa R., Shanafelt M. C., Allsup A., Soderberg C., Anzola J., Freitas V., Turck C., Steinman L., Peltz G. Preferential usage of T cell antigen receptor V region gene segment V beta 5.1 by Borrelia burgdorferi antigen-reactive T cell clones isolated from a patient with Lyme disease. J Immunol. 1993 May 1;150(9):4125–4135. [PubMed] [Google Scholar]
  18. Lengl-Janssen B., Strauss A. F., Steere A. C., Kamradt T. The T helper cell response in Lyme arthritis: differential recognition of Borrelia burgdorferi outer surface protein A in patients with treatment-resistant or treatment-responsive Lyme arthritis. J Exp Med. 1994 Dec 1;180(6):2069–2078. doi: 10.1084/jem.180.6.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lim L. C., England D. M., DuChateau B. K., Glowacki N. J., Creson J. R., Lovrich S. D., Callister S. M., Jobe D. A., Schell R. F. Development of destructive arthritis in vaccinated hamsters challenged with Borrelia burgdorferi. Infect Immun. 1994 Jul;62(7):2825–2833. doi: 10.1128/iai.62.7.2825-2833.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lim L. C., England D. M., Glowacki N. J., DuChateau B. K., Schell R. F. Involvement of CD4+ T lymphocytes in induction of severe destructive Lyme arthritis in inbred LSH hamsters. Infect Immun. 1995 Dec;63(12):4818–4825. doi: 10.1128/iai.63.12.4818-4825.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ma J., Gingrich-Baker C., Franchi P. M., Bulger P., Coughlin R. T. Molecular analysis of neutralizing epitopes on outer surface proteins A and B of Borrelia burgdorferi. Infect Immun. 1995 Jun;63(6):2221–2227. doi: 10.1128/iai.63.6.2221-2227.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matyniak J. E., Reiner S. L. T helper phenotype and genetic susceptibility in experimental Lyme disease. J Exp Med. 1995 Mar 1;181(3):1251–1254. doi: 10.1084/jem.181.3.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miller L. C., Lynch E. A., Isa S., Logan J. W., Dinarello C. A., Steere A. C. Balance of synovial fluid IL-1 beta and IL-1 receptor antagonist and recovery from Lyme arthritis. Lancet. 1993 Jan 16;341(8838):146–148. doi: 10.1016/0140-6736(93)90006-3. [DOI] [PubMed] [Google Scholar]
  24. Nocton J. J., Dressler F., Rutledge B. J., Rys P. N., Persing D. H., Steere A. C. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med. 1994 Jan 27;330(4):229–234. doi: 10.1056/NEJM199401273300401. [DOI] [PubMed] [Google Scholar]
  25. Schubach W. H., Mudri S., Dattwyler R. J., Luft B. J. Mapping antibody-binding domains of the major outer surface membrane protein (OspA) of Borrelia burgdorferi. Infect Immun. 1991 Jun;59(6):1911–1915. doi: 10.1128/iai.59.6.1911-1915.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sears J. E., Fikrig E., Nakagawa T. Y., Deponte K., Marcantonio N., Kantor F. S., Flavell R. A. Molecular mapping of Osp-A mediated immunity against Borrelia burgdorferi, the agent of Lyme disease. J Immunol. 1991 Sep 15;147(6):1995–2000. [PubMed] [Google Scholar]
  27. Shanafelt M. C., Anzola J., Soderberg C., Yssel H., Turck C. W., Peltz G. Epitopes on the outer surface protein A of Borrelia burgdorferi recognized by antibodies and T cells of patients with Lyme disease. J Immunol. 1992 Jan 1;148(1):218–224. [PubMed] [Google Scholar]
  28. Simon M. M., Nerz G., Kramer M. D., Hurtenbach U., Schaible U. E., Wallich R. The outer surface lipoprotein A of Borrelia burgdorferi provides direct and indirect augmenting/co-stimulatory signals for the activation of CD4+ and CD8+ T cells. Immunol Lett. 1995 Jun;46(3):137–142. [PubMed] [Google Scholar]
  29. Simon M. M., Schaible U. E., Kramer M. D., Eckerskorn C., Museteanu C., Müller-Hermelink H. K., Wallich R. Recombinant outer surface protein a from Borrelia burgdorferi induces antibodies protective against spirochetal infection in mice. J Infect Dis. 1991 Jul;164(1):123–132. doi: 10.1093/infdis/164.1.123. [DOI] [PubMed] [Google Scholar]
  30. Steere A. C., Levin R. E., Molloy P. J., Kalish R. A., Abraham J. H., 3rd, Liu N. Y., Schmid C. H. Treatment of Lyme arthritis. Arthritis Rheum. 1994 Jun;37(6):878–888. doi: 10.1002/art.1780370616. [DOI] [PubMed] [Google Scholar]
  31. Wilske B., Luft B., Schubach W. H., Zumstein G., Jauris S., Preac-Mursic V., Kramer M. D. Molecular analysis of the outer surface protein A (OspA) of Borrelia burgdorferi for conserved and variable antibody binding domains. Med Microbiol Immunol. 1992;181(4):191–207. doi: 10.1007/BF00215765. [DOI] [PubMed] [Google Scholar]
  32. Wucherpfennig K. W., Strominger J. L. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995 Mar 10;80(5):695–705. doi: 10.1016/0092-8674(95)90348-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES