Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B*2705-restricted CD8+ T-cells

Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B*2705-restricted CD8+ T-cells

Online publication: 04/08/2010 Journal: Journal of Virology


The association between HLA-B*2705 and immune control of HIV-1 has previously been linked to targeting of the HLA-B*2705-restricted Gag epitope, KRWIILGLNK, by CD8+ T-cells. In order to better define the mechanisms of HLA-B*2705 immune control of HIV, we first characterized the CD8+ T-cell response in 9 HAART-naïve B*2705-positive subjects. Unexpectedly, we observed a strong response in 8/9 subjects to an HLA-B*2705-restricted Pol epitope, KRKGGIGGY (KY9). The magnitude of the KY9 response was only marginally lower than that of the KK10-specific response (median 695 vs 867 SFC/million PBMC; NS), and viral escape mutants were observed in both KY9 and KK10, resulting from selection pressure driven by the respective CD8+ T-cell response. Comparing inhibition of viral replication by CD8+ T-cells specific for the Gag-KK10, Pol-KY9 and Vpr-VL9 HLAB* 2705-restricted epitopes, we observed a consistent hierarchy of antiviral efficacy (Gag-KK10 > Pol-KY9 > Vpr-VL9). This hierarchy was associated with early recognition of HIV-1 infected cells, within 6 hrs of infection, by KK10- and KY9-specific CD8+ T-cells, but not until 18 hrs post-infection by VL9-specific CD8+ Tcells. There was no association between antiviral efficacy and proliferative capacity, cytotoxicity, polyfunctionality or TcR avidity. These data are consistent with previous studies indicating an important role for the B*2705-Gag-KK10 response in control of HIV, but also suggest a previously unrecognized role played by the subdominant Polspecific KY9 response in HLA-B*2705-mediated control of HIV; and that recognition of HIV-infected cells by CD8+ T-cells early in the viral life-cycle may be important for viral containment in HIV-infected individuals.

Authors: Payne RP, Kløverpris H, Sacha JB, Brumme Z, Brumme C, Buus S, Sims S, Hickling S, Riddell L, Chen F, Luzzi G, Edwards A, Phillips R, Prado JG, Goulder PJ.

Subscribe to our newsletter

Back to Top
Irsi Caixa

Promoted by:

'La Caixa' Foundation Generalitat de Catalunya - Departament de Salut


HR Excellence in Research

Member of:


In cooperation with: