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 vitro1,2. 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 vitro4. 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.
Similar content being viewed by others
References
Walker, B. D. et al. Science 240, 64–66 (1988).
Nixon, D. F. et al. Nature 336, 484–486 (1988).
Nixon, D. F. & McMichael, A. J. AIDS 5, 1049–1059 (1991).
Phillips, R. E. et al. Nature 354, 453–459 (1991).
Jameson, S. C., Carbone, F. R. & Bevan, M. J. J. exp. Med. 177, 1541–1550 (1993).
Evavold, B. D., Sloan-Lancaster, J. & Allen, P. Immunol. Today 14, 602–609 (1993).
De Magristris, M. T. et al. Cell 68, 625–634 (1992).
Ostrov, D. J. et al. J. Immun. 150, 4277–4283 (1993).
Evavold, B. D. & Allen, P. M. Science 252, 1308–1310 (1991).
Racioppi, L. et al. J. exp. Med. 177, 1047–1060 (1993).
Myers, G. et al. (eds) Human retroviruses and AIDS (Theoretical Biology and Biophysics group T-10, Los Alamos, 1992).
Sutton, J. et al. Eur. J. Immun. 23, 447–453 (1993).
Hogquist, K. A. et al. Cell 76, 17–27 (1994).
Dougherty, J. P. & Temin, H. M. J. Virol. 62, 2817–2822 (1988).
Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbour Laboratory Press, New York, 1982).
Zhang, G. Q. et al. AIDS 5, 675–681 (1991).
Rowland-Jones, S. et al. Eur. J. Immun. 23, 1999–2004 (1993).
Mackett, M., Smith, G. L. & Moss, B. J. Virol. 49, 857–864 (1984).
Author information
Authors and Affiliations
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/369403a0
- Springer Nature Limited
This article is cited by
-
CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides
Nature Immunology (2023)
-
Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition
Molecular Therapy (2016)
-
A CD4+T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function
Retrovirology (2014)
-
Accelerated crossing of fitness valleys through division of labor and cheating in asexual populations
Scientific Reports (2012)
-
Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes
Immunologic Research (2011)