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. 1989 Mar 1;169(3):641–652. doi: 10.1084/jem.169.3.641

Fl-160. A surface antigen of Trypanosoma cruzi that mimics mammalian nervous tissue

PMCID: PMC2189289  PMID: 2466939

Abstract

Chagas' disease, caused by Trypanosoma cruzi, is an excellent model for autoimmune disease induced by an infectious agent. Transfer of T cells, directed against crossreactive antigens of T. cruzi and nervous tissue, have been shown to reproduce pathology found in chronic Chagas' disease. We used recombinant DNA technology to characterize one of these crossreactive antigens (Fl-160). We have cloned DNA from T. cruzi, which expresses a protein corresponding to a 160-kD protein found on the surface of the trypanosome, overlying the flagellum. This clone hybridizes to a 4.5-kb poly(A)+ RNA that is distributed in a differentiation-specific manner, suggesting expression of this protein is transcriptionally controlled. Antibodies to this protein crossreact with a 48-kD mammalian nervous tissue protein found in sciatic nerve, brain, and myenteric plexi of gut. The myenteric plexi are destroyed by inflammatory infiltrates in Chagas' disease, leading to the characteristic megaesophagus and megacolon Chagas' disease pathology. Thus, this antigen is a candidate antigen for autoimmune mimicry leading to nervous tissue pathology.

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Selected References

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  1. Acosta A. M., Santos-Buch C. A. Autoimmune myocarditis induced by Trypanosoma cruzi. Circulation. 1985 Jun;71(6):1255–1261. doi: 10.1161/01.cir.71.6.1255. [DOI] [PubMed] [Google Scholar]
  2. Cossio P. M., Diez C., Szarfman A., Kreutzer E., Candiolo B., Arana R. M. Chagasic cardiopathy. Demonstration of a serum gamma globulin factor which reacts with endocardium and vascular structures. Circulation. 1974 Jan;49(1):13–21. doi: 10.1161/01.cir.49.1.13. [DOI] [PubMed] [Google Scholar]
  3. De Titto E. H., Braun M., Lazzari J. O., Segura E. L. Cell-mediated reactivity against human and Trypanosoma cruzi antigens according to clinical status in Chagas' disease patients. Immunol Lett. 1985;9(5):249–254. doi: 10.1016/0165-2478(85)90002-1. [DOI] [PubMed] [Google Scholar]
  4. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  5. Hontebeyrie-Joskowicz M., Said G., Milon G., Marchal G., Eisen H. L3T4+ T cells able to mediate parasite-specific delayed-type hypersensitivity play a role in the pathology of experimental Chagas' disease. Eur J Immunol. 1987 Jul;17(7):1027–1033. doi: 10.1002/eji.1830170720. [DOI] [PubMed] [Google Scholar]
  6. Ishigatsubo Y., Steinberg A. D., Klinman D. M. Autoantibody production is associated with polyclonal B cell activation in autoimmune mice which express the lpr or gld genes. Eur J Immunol. 1988 Jul;18(7):1089–1093. doi: 10.1002/eji.1830180718. [DOI] [PubMed] [Google Scholar]
  7. Khoury E. L., Ritacco V., Cossio P. M., Laguens R. P., Szarfman A., Diez C., Arana R. M. Circulating antibodies to peripheral nerve in American trypanosomiasis (Chagas' disease). Clin Exp Immunol. 1979 Apr;36(1):8–15. [PMC free article] [PubMed] [Google Scholar]
  8. Klinman D. M., Steinberg A. D. Systemic autoimmune disease arises from polyclonal B cell activation. J Exp Med. 1987 Jun 1;165(6):1755–1760. doi: 10.1084/jem.165.6.1755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Markwell M. A., Fox C. F. Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril. Biochemistry. 1978 Oct 31;17(22):4807–4817. doi: 10.1021/bi00615a031. [DOI] [PubMed] [Google Scholar]
  10. Minoprio P. M., Eisen H., Forni L., D'Imperio Lima M. R., Joskowicz M., Coutinho A. Polyclonal lymphocyte responses to murine Trypanosoma cruzi infection. I. Quantitation of both T- and B-cell responses. Scand J Immunol. 1986 Dec;24(6):661–668. doi: 10.1111/j.1365-3083.1986.tb02185.x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Petry K., Voisin P., Baltz T. Complex lipids as common antigens to Trypanosoma cruzi, T. dionisii, T. vespertilionis and nervous tissue (astrocytes, neurons). Acta Trop. 1987 Dec;44(4):381–386. [PubMed] [Google Scholar]
  13. Petry K., Voisin P., Baltz T., Labouesse J. Epitopes common to trypanosomes (T. cruzi, T. dionisii and T. vespertilionis (Schizotrypanum)): astrocytes and neurons. J Neuroimmunol. 1987 Oct;16(2):237–252. doi: 10.1016/0165-5728(87)90078-6. [DOI] [PubMed] [Google Scholar]
  14. Plata F., Garcia Pons F., Eisen H. Antigenic polymorphism of Trypanosoma cruzi: clonal analysis of trypomastigote surface antigens. Eur J Immunol. 1984 May;14(5):392–399. doi: 10.1002/eji.1830140503. [DOI] [PubMed] [Google Scholar]
  15. Said G., Joskowicz M., Barreira A. A., Eisen H. Neuropathy associated with experimental Chagas' disease. Ann Neurol. 1985 Dec;18(6):676–683. doi: 10.1002/ana.410180609. [DOI] [PubMed] [Google Scholar]
  16. Snary D., Flint J. E., Wood J. N., Scott M. T., Chapman M. D., Dodd J., Jessell T. M., Miles M. A. A monoclonal antibody with specificity for Trypanosoma cruzi, central and peripheral neurones and glia. Clin Exp Immunol. 1983 Dec;54(3):617–624. [PMC free article] [PubMed] [Google Scholar]
  17. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Williams G. T., Fielder L., Smith H., Hudson L. Adsorption of Trypanosoma cruzi proteins to mammalian cells in vitro. Acta Trop. 1985 Mar;42(1):33–38. [PubMed] [Google Scholar]
  19. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. van de Rijn I., Zabriskie J. B., McCarty M. Group A streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen. J Exp Med. 1977 Aug 1;146(2):579–599. doi: 10.1084/jem.146.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]

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