Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1991 Feb;59(2):514–520. doi: 10.1128/iai.59.2.514-520.1991

Immunoreactive epitopes on an expressed recombinant flagellar protein of Borrelia burgdorferi.

C Collins 1, G Peltz 1
PMCID: PMC257779  PMID: 1702766

Abstract

A recombinant Borrelia burgdorferi flagellin protein expressed in Escherichia coli is bound by a murine monoclonal antiflagellin antibody (H9724) and by antibodies in the sera of patients with Lyme disease. Immunoreactive epitopes on the flagellar protein were identified by immunoblot analysis of antibody binding to expressed truncated flagellar proteins. The epitope recognized by the murine monoclonal antibody is within the central heterologous region of the flagellar protein (amino acids 90 to 266). However, antiflagellin antibodies in the sera of patients with Lyme arthritis bound an epitope entirely within, or whose conformation was partly formed by, the 90 NH2-terminal amino acids of the flagellar protein. The binding of antibodies in the sera of patients with Lyme arthritis to the NH2-terminal region of the flagellar protein, a region with sequence homology to the flagellar proteins of other bacterial species, suggests the possibility that antigenic mimicry contributes to the immunopathogenesis of Lyme disease. The fact that human antibodies bind to a highly conserved and hence shared portion of the flagellin reduces the specificity of serological assays for the diagnosis of Lyme disease which use the flagellar protein as antigen.

Full text

PDF
514

Images in this article

Selected References

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

  1. Aberer E., Brunner C., Suchanek G., Klade H., Barbour A., Stanek G., Lassmann H. Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdorferi and human tissue. Ann Neurol. 1989 Dec;26(6):732–737. doi: 10.1002/ana.410260608. [DOI] [PubMed] [Google Scholar]
  2. Barbour A. G., Burgdorfer W., Grunwaldt E., Steere A. C. Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete. J Clin Invest. 1983 Aug;72(2):504–515. doi: 10.1172/JCI110998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbour A. G., Hayes S. F., Heiland R. A., Schrumpf M. E., Tessier S. L. A Borrelia-specific monoclonal antibody binds to a flagellar epitope. Infect Immun. 1986 May;52(2):549–554. doi: 10.1128/iai.52.2.549-554.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barbour A. G. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521–525. [PMC free article] [PubMed] [Google Scholar]
  5. Barbour A. G. Laboratory aspects of Lyme borreliosis. Clin Microbiol Rev. 1988 Oct;1(4):399–414. doi: 10.1128/cmr.1.4.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barbour A. G. The diagnosis of Lyme disease: rewards and perils. Ann Intern Med. 1989 Apr 1;110(7):501–502. doi: 10.7326/0003-4819-110-7-501. [DOI] [PubMed] [Google Scholar]
  7. Burgdorfer W., Barbour A. G., Hayes S. F., Benach J. L., Grunwaldt E., Davis J. P. Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317–1319. doi: 10.1126/science.7043737. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Coleman J. L., Benach J. L. Identification and characterization of an endoflagellar antigen of Borrelia burgdorferi. J Clin Invest. 1989 Jul;84(1):322–330. doi: 10.1172/JCI114157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coleman J. L., Benach J. L. Isolation of antigenic components from the Lyme disease spirochete: their role in early diagnosis. J Infect Dis. 1987 Apr;155(4):756–765. doi: 10.1093/infdis/155.4.756. [DOI] [PubMed] [Google Scholar]
  11. Craft J. E., Fischer D. K., Shimamoto G. T., Steere A. C. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness. J Clin Invest. 1986 Oct;78(4):934–939. doi: 10.1172/JCI112683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ennis P. D., Zemmour J., Salter R. D., Parham P. Rapid cloning of HLA-A,B cDNA by using the polymerase chain reaction: frequency and nature of errors produced in amplification. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2833–2837. doi: 10.1073/pnas.87.7.2833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gassmann G. S., Kramer M., Göbel U. B., Wallich R. Nucleotide sequence of a gene encoding the Borrelia burgdorferi flagellin. Nucleic Acids Res. 1989 May 11;17(9):3590–3590. doi: 10.1093/nar/17.9.3590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hansen K., Hindersson P., Pedersen N. S. Measurement of antibodies to the Borrelia burgdorferi flagellum improves serodiagnosis in Lyme disease. J Clin Microbiol. 1988 Feb;26(2):338–346. doi: 10.1128/jcm.26.2.338-346.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Homma M., Fujita H., Yamaguchi S., Iino T. Regions of Salmonella typhimurium flagellin essential for its polymerization and excretion. J Bacteriol. 1987 Jan;169(1):291–296. doi: 10.1128/jb.169.1.291-296.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Joys T. M. The covalent structure of the phase-1 flagellar filament protein of Salmonella typhimurium and its comparison with other flagellins. J Biol Chem. 1985 Dec 15;260(29):15758–15761. [PubMed] [Google Scholar]
  17. Krug M. S., Berger S. L. First-strand cDNA synthesis primed with oligo(dT). Methods Enzymol. 1987;152:316–325. doi: 10.1016/0076-6879(87)52036-5. [DOI] [PubMed] [Google Scholar]
  18. Kuwajima G., Asaka J., Fujiwara T., Fujiwara T., Node K., Kondo E. Nucleotide sequence of the hag gene encoding flagellin of Escherichia coli. J Bacteriol. 1986 Dec;168(3):1479–1483. doi: 10.1128/jb.168.3.1479-1483.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kuwajima G. Construction of a minimum-size functional flagellin of Escherichia coli. J Bacteriol. 1988 Jul;170(7):3305–3309. doi: 10.1128/jb.170.7.3305-3309.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kuwajima G. Flagellin domain that affects H antigenicity of Escherichia coli K-12. J Bacteriol. 1988 Jan;170(1):485–488. doi: 10.1128/jb.170.1.485-488.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Logan S. M., Trust T. J., Guerry P. Evidence for posttranslational modification and gene duplication of Campylobacter flagellin. J Bacteriol. 1989 Jun;171(6):3031–3038. doi: 10.1128/jb.171.6.3031-3038.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Magnarelli L. A., Anderson J. F., Barbour A. G. Enzyme-linked immunosorbent assays for Lyme disease: reactivity of subunits of Borrelia burgdorferi. J Infect Dis. 1989 Jan;159(1):43–49. doi: 10.1093/infdis/159.1.43. [DOI] [PubMed] [Google Scholar]
  23. Mensi N., Webb D. R., Turck C. W., Peltz G. A. Characterization of Borrelia burgdorferi proteins reactive with antibodies in synovial fluid of a patient with Lyme arthritis. Infect Immun. 1990 Jul;58(7):2404–2407. doi: 10.1128/iai.58.7.2404-2407.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oldstone M. B. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  25. Pallesen L., Hindersson P. Cloning and sequencing of a Treponema pallidum gene encoding a 31.3-kilodalton endoflagellar subunit (FlaB2). Infect Immun. 1989 Jul;57(7):2166–2172. doi: 10.1128/iai.57.7.2166-2172.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yamaguchi S., Fujita H., Sugata K., Taira T., Iino T. Genetic analysis of H2, the structural gene for phase-2 flagellin in Salmonella. J Gen Microbiol. 1984 Feb;130(2):255–265. doi: 10.1099/00221287-130-2-255. [DOI] [PubMed] [Google Scholar]
  27. Yssel H., Nakamoto T., Schneider P., Freitas V., Collins C., Webb D., Mensi N., Soderberg C., Peltz G. Analysis of T lymphocytes cloned from the synovial fluid and blood of a patient with Lyme arthritis. Int Immunol. 1990;2(11):1081–1089. doi: 10.1093/intimm/2.11.1081. [DOI] [PubMed] [Google Scholar]

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

RESOURCES