Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants (original) (raw)

Nature volume 369, pages 403–407 (1994)Cite this article

Abstract

MOST asymptomatic individuals infected with HIV-1 have a cyto-toxic T lymphocyte (CTL) response to the virus Gag proteins which can be demonstrated _in vitro_1,2. Epitopes have been mapped in p17 Gag and p24 Gag restricted by HLA-B8 (p17-3 and p24-13) and -B27 (p24-14) 2,3. Viruses isolated from patients who make CTL responses to these peptides vary within the genetic sequences encoding these epitopes and some mutations lead to reduction in killing activity in _vitro_4. This was attributed to either failure of the variant epitope to bind major histocompatibility complex class I or failure of T-cell receptors to bind the presented peptide. But peptide variants of class I-restricted epitopes cause 'antagonism', that is, the presence of a variant epitope (in the form of peptide) inhibits normal lysis of targets presenting the original epitope5,6. This mirrors similar findings in class II-restricted systems7–10. Here we report that naturally occurring variant forms of p17-3, p24-13 and p24-14 may cause antagonism of CTL lines derived from the same individuals. The effect is present if the epitopes are derived from synthetic peptides and when they are processed from full-length proteins expressed by either recombinant vaccinia constructs or replicating HIV.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Walker, B. D. et al. Science 240, 64–66 (1988).
    Article ADS CAS Google Scholar
  2. Nixon, D. F. et al. Nature 336, 484–486 (1988).
    Article ADS CAS Google Scholar
  3. Nixon, D. F. & McMichael, A. J. AIDS 5, 1049–1059 (1991).
    CAS PubMed Google Scholar
  4. Phillips, R. E. et al. Nature 354, 453–459 (1991).
    Article ADS CAS Google Scholar
  5. Jameson, S. C., Carbone, F. R. & Bevan, M. J. J. exp. Med. 177, 1541–1550 (1993).
    Article CAS Google Scholar
  6. Evavold, B. D., Sloan-Lancaster, J. & Allen, P. Immunol. Today 14, 602–609 (1993).
    Article CAS Google Scholar
  7. De Magristris, M. T. et al. Cell 68, 625–634 (1992).
    Article Google Scholar
  8. Ostrov, D. J. et al. J. Immun. 150, 4277–4283 (1993).
    CAS PubMed Google Scholar
  9. Evavold, B. D. & Allen, P. M. Science 252, 1308–1310 (1991).
    Article ADS CAS Google Scholar
  10. Racioppi, L. et al. J. exp. Med. 177, 1047–1060 (1993).
    Article CAS Google Scholar
  11. Myers, G. et al. (eds) Human retroviruses and AIDS (Theoretical Biology and Biophysics group T-10, Los Alamos, 1992).
  12. Sutton, J. et al. Eur. J. Immun. 23, 447–453 (1993).
    Article CAS Google Scholar
  13. Hogquist, K. A. et al. Cell 76, 17–27 (1994).
    Article CAS Google Scholar
  14. Dougherty, J. P. & Temin, H. M. J. Virol. 62, 2817–2822 (1988).
    CAS PubMed PubMed Central Google Scholar
  15. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbour Laboratory Press, New York, 1982).
    Google Scholar
  16. Zhang, G. Q. et al. AIDS 5, 675–681 (1991).
    Article CAS Google Scholar
  17. Rowland-Jones, S. et al. Eur. J. Immun. 23, 1999–2004 (1993).
    Article CAS Google Scholar
  18. Mackett, M., Smith, G. L. & Moss, B. J. Virol. 49, 857–864 (1984).
    CAS PubMed PubMed Central Google Scholar

Download references

Author information

Author notes

  1. Anne Edwards: Genito-urinary Medicine Department, Radcliffe Infirmary, Woodstock Road, Oxford 0X3 7LJ, UK
  2. Paul Giangrande: Oxford Haemophilia Centre, Churchill Hospital, Oxford 0X3 7LV, UK

Authors and Affiliations

  1. Molecular Sciences Division, Nuffield Department of Clinical Medicine and Institute of Molecular Medicine, University of Oxford, Oxford, 0X3 9DU, UK
    Paul Klenerman, Sarah Rowland-Jones, Steve McAdam, Jon Edwards, Susan Daenke, David Lalloo, Britta Köppe, William Rosenberg, Diana Boyd, Anne Edwards, Paul Giangrande, Rodney E. Phillips & Andrew J. McMichael

Authors

  1. Paul Klenerman
    You can also search for this author inPubMed Google Scholar
  2. Sarah Rowland-Jones
    You can also search for this author inPubMed Google Scholar
  3. Steve McAdam
    You can also search for this author inPubMed Google Scholar
  4. Jon Edwards
    You can also search for this author inPubMed Google Scholar
  5. Susan Daenke
    You can also search for this author inPubMed Google Scholar
  6. David Lalloo
    You can also search for this author inPubMed Google Scholar
  7. Britta Köppe
    You can also search for this author inPubMed Google Scholar
  8. William Rosenberg
    You can also search for this author inPubMed Google Scholar
  9. Diana Boyd
    You can also search for this author inPubMed Google Scholar
  10. Anne Edwards
    You can also search for this author inPubMed Google Scholar
  11. Paul Giangrande
    You can also search for this author inPubMed Google Scholar
  12. Rodney E. Phillips
    You can also search for this author inPubMed Google Scholar
  13. Andrew J. McMichael
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Klenerman, P., Rowland-Jones, S., McAdam, S. et al. Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants.Nature 369, 403–407 (1994). https://doi.org/10.1038/369403a0

Download citation

This article is cited by