Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Jun;62(6):2483–2489. doi: 10.1128/iai.62.6.2483-2489.1994

A lytic monoclonal antibody to Trypanosoma cruzi bloodstream trypomastigotes which recognizes an epitope expressed in tissues affected in Chagas' disease.

N W Zwirner 1, E L Malchiodi 1, M G Chiaramonte 1, C A Fossati 1
PMCID: PMC186535  PMID: 7514576

Abstract

It has been suggested that molecular mimicry between the antigens of Trypanosoma cruzi and the host could have a role in the onset of the chronic stage of Chagas' disease. In this article, we report on a monoclonal antibody (MAb), CAK20.12 (immunoglobulin G2b), which reacts with a polypeptidic epitope of a 150-kDa antigen expressed on the surface of several strains of T. cruzi. This MAb also causes lysis of bloodstream trypomastigotes. Serum samples from 30 of 30 patients with chronic and 11 of 13 patients with acute Chagas' disease present specific antibodies to this antigen. MAb CAK20.12 reacts, by indirect immunofluorescence, with human and syngeneic murine striated muscle tissue, with the smooth muscle layer of cardiac arteries, with the lamina muscularis mucosae and the external striated muscle layer of the esophagus, and with the smooth muscle cells of the colon from normal syngeneic mice. Reactivity with the small intestine was very weak, and no reactivity with ventricle or atrium tissue was detected. Adsorption with an antigenic fraction from normal murine striated muscle or from T. cruzi epimastigotes confirmed that MAb CAK20.12 recognizes a common epitope present in parasites and host tissues. MAb CAK20.12, lytic for the infective form of T. cruzi, recognizes an epitope expressed in striated and smooth muscle cells of the host tissues affected in the chronic stage of Chagas' disease.

Full text

PDF
2483

Images in this article

2486Image
on p.2486
2487Image
on p.2487
2487Image
on p.2487

Selected References

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

  1. Alcina A., Fresno M. A tubulin-related 55 kilodalton surface antigen recognized by different Trypanosoma cruzi stage-specific monoclonal antibodies from infected mice. Mol Biochem Parasitol. 1988 Jun;29(2-3):181–190. doi: 10.1016/0166-6851(88)90073-4. [DOI] [PubMed] [Google Scholar]
  2. Alvarez M., Cerisola J. A., Rohwedder R. W. Test de inmunofluorescencia para diagnóstico de la enfermedad de Chagas. Bol Chil Parasitol. 1968 Jan-Jun;23(1):4–8. [PubMed] [Google Scholar]
  3. Appelmelk B. J., Verweij-Van Vught A. M., Maaskant J. J., Thijs L. G., MacLaren D. M. Murine ascitic fluids contain varying amounts of an inhibitor that interferes with complement-mediated effector functions of monoclonal antibodies. Immunol Lett. 1992 Jul;33(2):135–138. doi: 10.1016/0165-2478(92)90037-o. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Brener Z. Immunity to Trypanosoma cruzi. Adv Parasitol. 1980;18:247–292. doi: 10.1016/s0065-308x(08)60401-7. [DOI] [PubMed] [Google Scholar]
  6. Carbonetto C. H., Malchiodi E. L., Chiaramonte M., Durante de Isola E., Fossati C. A., Margni R. A. Isolation of a Trypanosoma cruzi antigen by affinity chromatography with a monoclonal antibody. Preliminary evaluation of its possible applications in serological tests. Clin Exp Immunol. 1990 Oct;82(1):93–96. doi: 10.1111/j.1365-2249.1990.tb05409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Celentano A. M., González Cappa S. M. Induction of macrophage activation and opsonizing antibodies by Trypanosoma cruzi subpopulations. Parasite Immunol. 1992 Mar;14(2):155–167. doi: 10.1111/j.1365-3024.1992.tb00458.x. [DOI] [PubMed] [Google Scholar]
  8. Cicarelli R. M., Lopes J. D. Characterization of a protein from Trypanosoma cruzi trypomastigotes that cleaves non-immune IgG bound through its Fab fragment. J Immunol. 1989 Mar 1;142(5):1685–1690. [PubMed] [Google Scholar]
  9. Fischer E., Ouaissi M. A., Velge P., Cornette J., Kazatchkine M. D. gp 58/68, a parasite component that contributes to the escape of the trypomastigote form of T. cruzi from damage by the human alternative complement pathway. Immunology. 1988 Oct;65(2):299–303. [PMC free article] [PubMed] [Google Scholar]
  10. Goldbaum F. A., Leoni J., Wallach J. C., Fossati C. A. Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis. J Clin Microbiol. 1993 Aug;31(8):2141–2145. doi: 10.1128/jcm.31.8.2141-2145.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. González Cappa S. M., Chiale P., del Prado G. E., Katzin A. M., de Martini G. W., de Isola E. D., Abramo Orrego L., Segura E. L. Aislamiento de uan cepa de Trypanosoma cruzi de un Paciente con miocardiopatía chagásica cronica y su caracterización biológica. Medicina (B Aires) 1980;40 (Suppl 1):63–68. [PubMed] [Google Scholar]
  12. Hudson L. Autoimmune phenomena in chronic chagasic cardiopathy. Parasitol Today. 1985 Jul;1(1):6–9. doi: 10.1016/0169-4758(85)90099-7. [DOI] [PubMed] [Google Scholar]
  13. Hudson L., Guhl F., Marinkelle C. J., Rodriguez J. Use of monoclonal antibodies for the differential detection of Trypanosoma cruzi and T. rangeli in epidemiological studies and xenodiagnosis. Acta Trop. 1987 Dec;44(4):387–394. [PubMed] [Google Scholar]
  14. Joiner K. A., daSilva W. D., Rimoldi M. T., Hammer C. H., Sher A., Kipnis T. L. Biochemical characterization of a factor produced by trypomastigotes of Trypanosoma cruzi that accelerates the decay of complement C3 convertases. J Biol Chem. 1988 Aug 15;263(23):11327–11335. [PubMed] [Google Scholar]
  15. Kierszenbaum F. Autoimmunity in Chagas' disease. J Parasitol. 1986 Apr;72(2):201–211. [PubMed] [Google Scholar]
  16. Kierszenbaum F., Lima M. F. Susceptibility of insect-borne, metacyclic forms of Trypanosoma cruzi to antibody-mediated mechanisms of destruction. Am J Trop Med Hyg. 1983 Nov;32(6):1236–1241. doi: 10.4269/ajtmh.1983.32.1236. [DOI] [PubMed] [Google Scholar]
  17. Kipnis T. L., da Silva W. D. Evasion of Trypanosoma cruzi from complement lysis. Braz J Med Biol Res. 1989;22(1):1–16. [PubMed] [Google Scholar]
  18. Krettli A. U., Brener Z. Protective effects of specific antibodies in Trypanosoma cruzi infections. J Immunol. 1976 Mar;116(3):755–760. [PubMed] [Google Scholar]
  19. Krettli A. U., Brener Z. Resistance against Trypanosoma cruzi associated to anti-living trypomastigote antibodies. J Immunol. 1982 May;128(5):2009–2012. [PubMed] [Google Scholar]
  20. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  21. Levin M. J., Mesri E., Benarous R., Levitus G., Schijman A., Levy-Yeyati P., Chiale P. A., Ruiz A. M., Kahn A., Rosenbaum M. B. Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease. Am J Trop Med Hyg. 1989 Nov;41(5):530–538. doi: 10.4269/ajtmh.1989.41.530. [DOI] [PubMed] [Google Scholar]
  22. Mortara R. A. Studies on trypanosomatid actin. I. Immunochemical and biochemical identification. J Protozool. 1989 Jan-Feb;36(1):8–13. doi: 10.1111/j.1550-7408.1989.tb02666.x. [DOI] [PubMed] [Google Scholar]
  23. Norris K. A., Harth G., So M. Purification of a Trypanosoma cruzi membrane glycoprotein which elicits lytic antibodies. Infect Immun. 1989 Aug;57(8):2372–2377. doi: 10.1128/iai.57.8.2372-2377.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Paulin J. J., Keith C. H., Tarleton R. L. A monoclonal antibody to alpha tubulin recognizes host cell and Trypanosoma cruzi tubulins. J Protozool. 1988 Feb;35(1):123–129. doi: 10.1111/j.1550-7408.1988.tb04091.x. [DOI] [PubMed] [Google Scholar]
  25. Prioli R. P., Mejia J. S., Pereira M. E. Monoclonal antibodies against Trypanosoma cruzi neuraminidase reveal enzyme polymorphism, recognize a subset of trypomastigotes, and enhance infection in vitro. J Immunol. 1990 Jun 1;144(11):4384–4391. [PubMed] [Google Scholar]
  26. Sadigursky M., Acosta A. M., Santos-Buch C. A. Muscle sarcoplasmic reticulum antigen shared by a Trypanosoma cruzi clone. Am J Trop Med Hyg. 1982 Sep;31(5):934–941. doi: 10.4269/ajtmh.1982.31.934. [DOI] [PubMed] [Google Scholar]
  27. Schenkman S., Güther M. L., Yoshida N. Mechanism of resistance to lysis by the alternative complement pathway in Trypanosoma cruzi trypomastigotes: effect of specific monoclonal antibody. J Immunol. 1986 Sep 1;137(5):1623–1628. [PubMed] [Google Scholar]
  28. Segura E. L., Bua J., Rosenstein de Campanini A., Subias E., Esteva M., Moreno M., Ruiz A. M. Monoclonal antibodies against the flagellar fraction of epimastigotes of Trypanosoma cruzi: complement-mediated lytic activity against trypomastigotes and passive immunoprotection in mice. Immunol Lett. 1986 Oct;13(4):165–171. doi: 10.1016/0165-2478(86)90050-7. [DOI] [PubMed] [Google Scholar]
  29. Skeiky Y. A., Benson D. R., Parsons M., Elkon K. B., Reed S. G. Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients. J Exp Med. 1992 Jul 1;176(1):201–211. doi: 10.1084/jem.176.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Szarfman A., Terranova V. P., Rennard S. I., Foidart J. M., de Fatima Lima M., Scheinman J. I., Martin G. R. Antibodies to laminin in Chagas' disease. J Exp Med. 1982 Apr 1;155(4):1161–1171. doi: 10.1084/jem.155.4.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Takehara H. A., Perini A., da Silva M. H., Mota I. Trypanosoma cruzi: role of different antibody classes in protection against infection in the mouse. Exp Parasitol. 1981 Aug;52(1):137–146. doi: 10.1016/0014-4894(81)90069-2. [DOI] [PubMed] [Google Scholar]
  33. Tambourgi D. V., Kipnis T. L., da Silva W. D., Joiner K. A., Sher A., Heath S., Hall B. F., Ogden G. B. A partial cDNA clone of trypomastigote decay-accelerating factor (T-DAF), a developmentally regulated complement inhibitor of Trypanosoma cruzi, has genetic and functional similarities to the human complement inhibitor DAF. Infect Immun. 1993 Sep;61(9):3656–3663. doi: 10.1128/iai.61.9.3656-3663.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Teixeira M. M., Yoshida N. Stage-specific surface antigens of metacyclic trypomastigotes of Trypanosoma cruzi identified by monoclonal antibodies. Mol Biochem Parasitol. 1986 Mar;18(3):271–282. doi: 10.1016/0166-6851(86)90085-x. [DOI] [PubMed] [Google Scholar]
  35. Tsang V. C., Peralta J. M., Simons A. R. Enzyme-linked immunoelectrotransfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol. 1983;92:377–391. doi: 10.1016/0076-6879(83)92032-3. [DOI] [PubMed] [Google Scholar]
  36. Van Voorhis W. C., Eisen H. Fl-160. A surface antigen of Trypanosoma cruzi that mimics mammalian nervous tissue. J Exp Med. 1989 Mar 1;169(3):641–652. doi: 10.1084/jem.169.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Vennegoor C., Calafat J., Hageman P., van Buitenen F., Janssen H., Kolk A., Rümke P. Biochemical characterization and cellular localization of a formalin-resistant melanoma-associated antigen reacting with monoclonal antibody NKI/C-3. Int J Cancer. 1985 Mar 15;35(3):287–295. doi: 10.1002/ijc.2910350302. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Wood J. N., Hudson L., Jessell T. M., Yamamoto M. A monoclonal antibody defining antigenic determinants on subpopulations of mammalian neurones and Trypanosoma cruzi parasites. Nature. 1982 Mar 4;296(5852):34–38. doi: 10.1038/296034a0. [DOI] [PubMed] [Google Scholar]
  40. Yoshida N., Mortara R. A., Araguth M. F., Gonzalez J. C., Russo M. Metacyclic neutralizing effect of monoclonal antibody 10D8 directed to the 35- and 50-kilodalton surface glycoconjugates of Trypanosoma cruzi. Infect Immun. 1989 Jun;57(6):1663–1667. doi: 10.1128/iai.57.6.1663-1667.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES