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. 1992 Feb 15;89(4):1239–1243. doi: 10.1073/pnas.89.4.1239

Identification and synthesis of a major conserved antigenic epitope of Trypanosoma cruzi.

J M Burns Jr 1, W G Shreffler 1, D E Rosman 1, P R Sleath 1, C J March 1, S G Reed 1
PMCID: PMC48424  PMID: 1371355

Abstract

A gene sequence encoding an immunodominant protein with a repetitive epitope from the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, was cloned and expressed. The identified 10-amino acid repeat is present within a high-molecular-weight trypomastigote antigen that appears specific to and conserved among T. cruzi isolates. More importantly, greater than 95% of T. cruzi infection sera, including both chronic and acute Chagas disease, contained elevated levels of antibody to a 15-amino acid synthetic peptide bearing the repetitive B-cell epitope. Considering the wide diversity of T. cruzi parasites, as well as the broad spectrum of clinical manifestations of Chagas disease, such a prevalent immune response among patients is significant and applicable to the control of Chagas disease through the diagnosis of T. cruzi infection.

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Selected References

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  1. Affranchino J. L., Ibañez C. F., Luquetti A. O., Rassi A., Reyes M. B., Macina R. A., Aslund L., Pettersson U., Frasch A. C. Identification of a Trypanosoma cruzi antigen that is shed during the acute phase of Chagas' disease. Mol Biochem Parasitol. 1989 May 15;34(3):221–228. doi: 10.1016/0166-6851(89)90050-9. [DOI] [PubMed] [Google Scholar]
  2. Avila H., Goncalves A. M., Nehme N. S., Morel C. M., Simpson L. Schizodeme analysis of Trypanosoma cruzi stocks from South and Central America by analysis of PCR-amplified minicircle variable region sequences. Mol Biochem Parasitol. 1990 Sep-Oct;42(2):175–187. doi: 10.1016/0166-6851(90)90160-n. [DOI] [PubMed] [Google Scholar]
  3. Dragon E. A., Brothers V. M., Wrightsman R. A., Manning J. A Mr 90 000 surface polypeptide of Trypanosoma cruzi as a candidate for a Chagas' disease diagnostic antigen. Mol Biochem Parasitol. 1985 Sep;16(3):213–229. doi: 10.1016/0166-6851(85)90065-9. [DOI] [PubMed] [Google Scholar]
  4. Dvorak J. A., Engel J. C., Leapman R. D., Swyt C. R., Pella P. A. Trypanosoma cruzi: elemental composition heterogeneity of cloned stocks. Mol Biochem Parasitol. 1988 Oct;31(1):19–26. doi: 10.1016/0166-6851(88)90141-7. [DOI] [PubMed] [Google Scholar]
  5. Frasch A. C., Reyes M. B. Diagnosis of Chagas disease using recombinant DNA technology. Parasitol Today. 1990 Apr;6(4):137–139. doi: 10.1016/0169-4758(90)90234-u. [DOI] [PubMed] [Google Scholar]
  6. Grant I. H., Gold J. W., Wittner M., Tanowitz H. B., Nathan C., Mayer K., Reich L., Wollner N., Steinherz L., Ghavimi F. Transfusion-associated acute Chagas disease acquired in the United States. Ann Intern Med. 1989 Nov 15;111(10):849–851. doi: 10.7326/0003-4819-111-10-849. [DOI] [PubMed] [Google Scholar]
  7. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  8. Hoft D. F., Kim K. S., Otsu K., Moser D. R., Yost W. J., Blumin J. H., Donelson J. E., Kirchhoff L. V. Trypanosoma cruzi expresses diverse repetitive protein antigens. Infect Immun. 1989 Jul;57(7):1959–1967. doi: 10.1128/iai.57.7.1959-1967.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ibañez C. F., Affranchino J. L., Frasch A. C. Antigenic determinants of Trypanosoma cruzi defined by cloning of parasite DNA. Mol Biochem Parasitol. 1987 Sep;25(2):175–184. doi: 10.1016/0166-6851(87)90006-5. [DOI] [PubMed] [Google Scholar]
  10. Ibañez C. F., Affranchino J. L., Macina R. A., Reyes M. B., Leguizamon S., Camargo M. E., Aslund L., Pettersson U., Frasch A. C. Multiple Trypanosoma cruzi antigens containing tandemly repeated amino acid sequence motifs. Mol Biochem Parasitol. 1988 Jul;30(1):27–33. doi: 10.1016/0166-6851(88)90129-6. [DOI] [PubMed] [Google Scholar]
  11. Kemp D. J., Coppel R. L., Anders R. F. Repetitive proteins and genes of malaria. Annu Rev Microbiol. 1987;41:181–208. doi: 10.1146/annurev.mi.41.100187.001145. [DOI] [PubMed] [Google Scholar]
  12. Kirchhoff L. V., Gam A. A., Gusmao R. A., Goldsmith R. S., Rezende J. M., Rassi A. Increased specificity of serodiagnosis of Chagas' disease by detection of antibody to the 72- and 90-kilodalton glycoproteins of Trypanosoma cruzi. J Infect Dis. 1987 Mar;155(3):561–564. doi: 10.1093/infdis/155.3.561. [DOI] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Lafaille J. J., Linss J., Krieger M. A., Souto-Padrón T., de Souza W., Goldenberg S. Structure and expression of two Trypanosoma cruzi genes encoding antigenic proteins bearing repetitive epitopes. Mol Biochem Parasitol. 1989 Jun 15;35(2):127–136. doi: 10.1016/0166-6851(89)90115-1. [DOI] [PubMed] [Google Scholar]
  15. McCutchan T. F., de la Cruz V. F., Good M. F., Wellems T. E. Antigenic diversity in Plasmodium falciparum. Prog Allergy. 1988;41:173–192. doi: 10.1159/000415223. [DOI] [PubMed] [Google Scholar]
  16. Miles M. A., Souza A., Povoa M., Shaw J. J., Lainson R., Toye P. J. Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil. Nature. 1978 Apr 27;272(5656):819–821. doi: 10.1038/272819a0. [DOI] [PubMed] [Google Scholar]
  17. Paranhos G. S., Cotrim P. C., Mortara R. A., Rassi A., Corral R., Freilij H. L., Grinstein S., Wanderley J., Camargo M. E., da Silveira J. F. Trypanosoma cruzi: cloning and expression of an antigen recognized by acute and chronic human chagasic sera. Exp Parasitol. 1990 Oct;71(3):284–293. doi: 10.1016/0014-4894(90)90033-9. [DOI] [PubMed] [Google Scholar]
  18. Reed S. G., Carvalho E. M., Sherbert C. H., Sampaio D. P., Russo D. M., Bacelar O., Pihl D. L., Scott J. M., Barral A., Grabstein K. H. In vitro responses to Leishmania antigens by lymphocytes from patients with leishmaniasis or Chagas' disease. J Clin Invest. 1990 Mar;85(3):690–696. doi: 10.1172/JCI114493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reed S. G., Shreffler W. G., Burns J. M., Jr, Scott J. M., Orge M. da G., Ghalib H. W., Siddig M., Badaro R. An improved serodiagnostic procedure for visceral leishmaniasis. Am J Trop Med Hyg. 1990 Dec;43(6):632–639. doi: 10.4269/ajtmh.1990.43.632. [DOI] [PubMed] [Google Scholar]
  20. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scharfstein J., Luquetti A., Murta A. C., Senna M., Rezende J. M., Rassi A., Mendonça-Previato L. Chagas' disease: serodiagnosis with purified Gp25 antigen. Am J Trop Med Hyg. 1985 Nov;34(6):1153–1160. doi: 10.4269/ajtmh.1985.34.1153. [DOI] [PubMed] [Google Scholar]
  22. Schechter M., Flint J. E., Voller A., Guhl F., Marinkelle C. J., Miles M. A. Purified Trypanosoma cruzi specific glycoprotein for discriminative serological diagnosis of South American trypanosomiasis (Chagas' disease). Lancet. 1983 Oct 22;2(8356):939–941. doi: 10.1016/s0140-6736(83)90453-1. [DOI] [PubMed] [Google Scholar]
  23. Schmuñis G. A. Trypanosoma cruzi, the etiologic agent of Chagas' disease: status in the blood supply in endemic and nonendemic countries. Transfusion. 1991 Jul-Aug;31(6):547–557. doi: 10.1046/j.1537-2995.1991.31691306255.x. [DOI] [PubMed] [Google Scholar]
  24. Tibayrenc M., Ward P., Moya A., Ayala F. J. Natural populations of Trypanosoma cruzi, the agent of Chagas disease, have a complex multiclonal structure. Proc Natl Acad Sci U S A. 1986 Jan;83(1):115–119. doi: 10.1073/pnas.83.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Trischmann T. M., Bloom B. R. Genetics of murine resistance to Trypanosoma cruzi. Infect Immun. 1982 Feb;35(2):546–551. doi: 10.1128/iai.35.2.546-551.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wrightsman R., Krassner S., Watson J. Genetic control of responses to Trypanosoma cruzi in mice: multiple genes influencing parasitemia and survival. Infect Immun. 1982 May;36(2):637–644. doi: 10.1128/iai.36.2.637-644.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

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