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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-43. A hierarchy of antiviral activity between different epitope-specific CD8+ T cells can be attributed to early elimination of HIV-infected cells

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Background

It has been hypothesised that the slow progression to AIDS exhibited by HLA-B*2705+ HIV-infected individuals is due to the immunodominant B*27-restricted response towards the p24 Gag epitope KK10 (Gag residues 263–272). This study aims to discern the contributing correlates of immune protection in HLA-B*2705+ HIV-infected individuals by comparing CD8+ T cell epitope specificity, cytokine profile, granzyme production and the kinetics of epitope presentation.

Methods

HLA-B*2705 MHC-I tetramers were used to enrich CD8+ T cell lines (>98% specific), specific for the Gag epitope KK10, the Vpr epitope VL9, and Pol epitope KY9. We compared the polyfunctionality, proliferation, granzyme production and specific killing capacity of these epitope-specific CD8+ T cells. We also compared the polyfunctionality and granzyme production of epitope-specific CD8+ T cells directly from ex vivo PBMCs. We then compared the ability of the different B*2705-restricted epitope specific CD8+ T cell lines (>98% specific) to suppress viral replication in vitro. HIV-permissive cells expressing B*2705 were infected and cocultured with the CD8+ T cells, firstly by synchronized magnetofection™ and monitored over 24 hours and secondly by 'natural' infection and monitored over 5–10 days.

Results

The Gag KK10- and Pol KY9-specific CD8+ T cells could elicit antiviral activity by 6 hours post-infection whereas the Vpr VL9-specific CD8+ T cells didn't elicit antiviral activity until 18 hours post-infection. We observed a clear hierarchy of antiviral potency dictated by epitope or HIV protein specificity (Gag KK10>Pol KY9>Vpr VL9). Antiviral activity did not correlate with polyfunctionality, proliferation, granzyme production or killing capacity.

Conclusion

The potent antiviral activity displayed by Gag KK10-specific CD8+ T cells may be due to early presentation of Gag epitopes on HIV-infected cells. A vaccine which promotes CD8+ T cells which can elicit early antiviral activity may help prevent viral dissemination during HIV infection and is a rational approach to vaccine design.

Author information

Correspondence to RP Payne.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Payne, R., Kloverpris, H., Garcia-Prado, J. et al. P16-43. A hierarchy of antiviral activity between different epitope-specific CD8+ T cells can be attributed to early elimination of HIV-infected cells. Retrovirology 6, P272 (2009). https://doi.org/10.1186/1742-4690-6-S3-P272

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Keywords

  • Antiviral Activity
  • Potent Antiviral Activity
  • Specific Killing
  • Early Elimination
  • Killing Capacity