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Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria

Nature volume 341, pages 323–326 (1989)Cite this article

Abstract

PROTECTIVE immunity against malaria is induced by vaccination of hosts with irradiation-attenuated sporozoites. This immunity is mediated in part by neutralizing antibodies that are directed mainly against the repeat domain of the circumsporozoite protein1–4. Early experiments showed, however, that B-cell-depleted mice that are immunized with sporozoites can resist challenge, indicating that T-cell effector mechanisms may also have a role in protection5. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CDS antigen (CD8+ T cells) 6,7, whose target is probably the developing liver-stage parasites8–10. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies11. Here we report the identification of an epitope contained within amino acids 249–260 of the Plasmodium berghei circumsporozoite protein that is recognized by H–2Kd-restricted cytotoxic T cells12,13. Passive transfer into mice of cytotoxic-T-cell clones that recognize this epitope conferred a high degree of protection against challenge. These results provide the first direct evidence that CD8+ T cells that are specific for a defined epitope can confer protection against a parasitic infection.

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References

  1. Nussenzweig, V. & Nussenzweig, R. S. Adv. Immun. 45, 283–322 (1989).

    Article  CAS  Google Scholar 

  2. Potocnjak, P. et al. J. exp. Med. 151, 1504–1513 (1980).

    Article  CAS  Google Scholar 

  3. Hollingdale, M. R., Zavala, F., Nussenzweig, R. S. & Nussenzweig, V. J. Immun. 128, 1929–1930 (1982).

    CAS  PubMed  Google Scholar 

  4. Charoenvit, Y., Leef, M. F., Yuan, L. F., Sedegah, M. & Beaudoin, R. L. Infect. Immunity 55, 604–608 (1987).

    CAS  Google Scholar 

  5. Chen, D. H., Tigelaar, R. E., & Weinbaum, F. I. J. Immun. 118, 1322–1327 (1977).

    CAS  PubMed  Google Scholar 

  6. Schofield, L. et al. Nature 330, 664–666 (1987).

    Article  ADS  CAS  Google Scholar 

  7. Weiss, W. R. et al. Proc. natn. Acad. Sci. U.S.A. 85, 573–576 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Ferreira, A. et al. Science 232, 881–884 (1986).

    Article  ADS  CAS  Google Scholar 

  9. Maheshwari, R. K. et al. Infect. Immunity 53, 628–629 (1986).

    CAS  Google Scholar 

  10. Hoffman, S. L. et al. Science 244, 1078–1081 (1989).

    Article  ADS  CAS  Google Scholar 

  11. Sadoff, J. C. et al. Science 240, 336–338 (1988).

    Article  ADS  CAS  Google Scholar 

  12. Eichinger, D. J., Arnot, D. E., Tam, J. P., Nussenzweig, V. & Enea, V. Molec. cell. Biol. 6, 3965–3972 (1986).

    Article  CAS  Google Scholar 

  13. Weber, J. L. et al. Expl. Parasit. 63, 295–300 (1987).

    Article  CAS  Google Scholar 

  14. Townsend, A. R. M. & Bodmer, H. A. Rev. Immun. 7, 601–624 (1989).

    Article  CAS  Google Scholar 

  15. Lal, A. A. et al. J. biol. Chem. 262, 2937–2940 (1987).

    CAS  PubMed  Google Scholar 

  16. Braciale, T. J., Sweetser, M. T., Morrison, L. A., Kittlesen, D. J. & Braciale, V. L. Proc. natn. Acad. Sci. U.S.A. 86, 277–281 (1989).

    Article  ADS  CAS  Google Scholar 

  17. Maryanski, J. L., Pala, P., Corradin, G. P., Jordan, B. R. & Cerottini, J. C. Nature 324, 578–579 (1986).

    Article  ADS  CAS  Google Scholar 

  18. Oldstone, M. B. A., Whitton, J. L., Lewicki, H. & Tishon, A. J. exp. Med. 168, 559–570 (1988).

    Article  CAS  Google Scholar 

  19. Takahashi, H. et al. Proc. natn. Acad. Sci. U.S.A. 85, 3105–3109 (1988).

    Article  ADS  CAS  Google Scholar 

  20. Bodmer, H. C., Pemberton, R. M., Rothbard, J. B. & Askonas, B. A. Cell 52, 253–258 (1988).

    Article  CAS  Google Scholar 

  21. Kumar, S. et al. Nature 334, 258–260 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Maryanski, J. L., Accolla, R. S. & Jordan, B. J. Immun. 136, 4340–4347 (1986).

    CAS  Google Scholar 

  23. Taylor, P. M. & Askonas, B. A. Eur. J. Immun. 13, 707–711 (1983).

    Article  CAS  Google Scholar 

  24. Dailay, M. O., Fathman, G., Butcher, E. C., Pillemer, E. & Weissman, I. J. Immun. 128, 2134–2136 (1982).

    Google Scholar 

  25. Carbone, F., Moore, M., Sheil, J. & Bevan, M. J. exp. Med. 167, 1767–1779 (1988).

    Article  CAS  Google Scholar 

  26. Townsend, A. et al. J. exp. Med. 168, 1211–1224 (1988).

    Article  CAS  Google Scholar 

  27. Taylor, P. M. & Askonas, B. A. Immunology 58, 417–420 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. de la Cruz, V., Lal, A. A. & McCutchan, T. F. Molec. biochem. Parasit. 28, 31–38 (1988).

    Article  CAS  Google Scholar 

  29. Romero, P. J. et al. Eur. J. Immun. 18, 1951–1957 (1988).

    Article  CAS  Google Scholar 

  30. Schreiber, R. D., Hicks, L. J., Celada, A., Buchmeier, N. A. & Gray, P. W. J. Immun. 134, 1609–1613 (1985).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York, 10016, USA

    Pedro Romero, Ruth S. Nussenzweig & Fidel Zavala

  2. Ludwig Institute for Cancer Research, Lausanne Branch, 1066, Epalinges, Switzerland

    Janet L. Maryanski

  3. Institute of Biochemistry, University of Lausanne, 1066, Epalinges, Switzerland

    Giampietro Corradin

  4. Department of Pathology and Kaplan Cancer Center, New York University School of Medicine, New York, New York, 10016, USA

    Victor Nussenzweig

Authors
  1. Pedro Romero
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  2. Janet L. Maryanski
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  3. Giampietro Corradin
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  4. Ruth S. Nussenzweig
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  5. Victor Nussenzweig
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  6. Fidel Zavala
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Romero, P., Maryanski, J., Corradin, G. et al. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature 341, 323–326 (1989). https://doi.org/10.1038/341323a0

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