Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Antigenic oscillations and shifting immunodominance in HIV-1 infections

Nature volume 375, pages 606–611 (1995)Cite this article

Abstract

ATYPICAL protein antigen contains several epitopes that can be recognized by cytotoxic T lymphocytes (CTL), but in a characteristic antiviral immune response in vivo, CTL recognize only a small number of these potential epitopes, sometimes only one1–2, this phenomenon is known as immunodominance1–10. Antigenic variation within CTL epitopes has been demonstrated for the human immunodeficiency virus HIV-1 (ref. 11) and other viruses12–7 and such 'antigenic escape' may be responsible for viral persistence. Here we develop a new mathematical model that deals with the interaction between CTL and multiple epitopes of a genetically variable pathogen, and show that the nonlinear competition among CTL responses against different epitopes can explain immunodominance. This model suggests that an antigenically homogeneous pathogen population tends to induce a dominant response against a single epitope, whereas a heterogeneous pathogen population can stimulate complicated fluctuating responses against multiple epitopes. Antigenic variation in the immunodominant epitope can shift responses to weaker epitopes and thereby reduce immuno-logical control of the pathogen population. These ideas are consistent with detailed longitudinal studies of CTL responses in HIV-1 infected patients. For vaccine design, the model suggests that the major response should be directed against conserved epitopes even if they are subdominant.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hill, A. B. et al. Immun. Rev. 133, 75–91 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Townsend, A. & Bodmer, H. A. Rev. Immun. 7, 601–633 (1989).

    Article  CAS  Google Scholar 

  3. Adorini, L. et al. J. exp. Med. 168, 2091–2104 (1988).

    Article  CAS  PubMed  Google Scholar 

  4. Liu, Z. et al. J. Immun. 151, 1852–1858 (1993).

    CAS  PubMed  Google Scholar 

  5. Sercarz, E. E. et al. A. Rev. Immun. 11, 729–766 (1993).

    Article  CAS  Google Scholar 

  6. Buus, S. et al. Science 235, 1353–1358 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Schaeffer, E. B. et al. Proc. natn. Acad. Sci. U.S.A. 86, 4649–4653 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Zinkernagel, R. M. et al. J. exp. Med. 148, 592–606 (1978).

    Article  CAS  PubMed  Google Scholar 

  9. Takahashi, H. et al. Science 246, 118–121 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Gegin, C. & Lehmann-Grube, F. J. Immun. 149, 3331–3338 (1992).

    CAS  PubMed  Google Scholar 

  11. Phillips, R. E. et al. Nature 354, 453–459 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Aebischer, T. et al. Proc. natn. Acad. Sci. U.S.A. 88, 11047–11051 (1991).

    Article  ADS  CAS  Google Scholar 

  13. Klenerman, P. et al. Nature 369, 403–407 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Niewiesk, S. et al. J. Virol. 69, 2649–2653 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Campos-Lima, P. et al. Science 260, 98–100 (1993).

    Article  ADS  PubMed  Google Scholar 

  16. Bertoletti, A. et al. Nature 369, 407–410 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Moskophidids, D. & Zinkernagel, R. M. J. Virol. 69, 2187–2193 (1995).

    Google Scholar 

  18. Nixon, D. F. et al. Nature 336, 484–487 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Walker, B. D. Science 240, 64–66 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. McMichael, A. J. & Walker, B. D. AIDS 8, S155–S174 (1994).

    Google Scholar 

  21. Koup, R. A. et al. J. Virol. 68, 4650–4655 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Safrit, J. T. et al. J. exp. Med. 179, 463–472 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Pantaleo, G. et al. Nature 370, 463–467 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Nowak, M. A., May, R. M., Sigmund, K. J. theor. Biol. (in the press).

  25. Bangham, C. R. M. & McMichael, A. J. in T-cell Immunity to Viruses in T Cells (eds Feldmann, M., Lamb, J., Owen, M. J.) 281–310 (Wiley, New York, 1989).

    Google Scholar 

  26. Carpenter, S. in Applied Virology Research 2. Virus Variability, Epidemiology, and control (eds Kurstak, E., Marusyk, R. G., Murphy, F. A. & van Regenmortel, H. V.) 99–115 (Plenum Medical Book Company, New York and London, 1990).

    Book  Google Scholar 

  27. Nowak, M. A. et al. Science 254, 963–969 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Nowak, M. A. & May, R. M. AIDS 7 (suppl. 1), S3–S18 (1993).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Zoology, University of Oxford, South Parks Road, 0X1 3PS, Oxford, UK

    Martin A. Nowak & Robert M. May

  2. Molecular Immunology Group, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, 0X3 9DU, UK

    Rodney E. Phillips, Sarah Rowland-Jones, David G. Lalloo, Steven McAdam, Paul Klenerman, Britta Köppe, Charles R. M. Bangham & Andrew J. McMichael

  3. Institut für Mathematik, Universität Wien, Strudlhofgasse 4, A-1090, Wien, Austria

    Karl Sigmund

Authors
  1. Martin A. Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert M. May
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rodney E. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sarah Rowland-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David G. Lalloo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steven McAdam
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Klenerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Britta Köppe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Karl Sigmund
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Charles R. M. Bangham
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Andrew J. McMichael
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nowak, M., May, R., Phillips, R. et al. Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature 375, 606–611 (1995). https://doi.org/10.1038/375606a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/375606a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing