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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B*2705-restricted CD8
+
T cells
Journal of Virology, Volume 84, No. 20, Year 2010
Notification
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Description
The association between HLA-B*2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B*2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8+ T cells. In order to better define the mechanisms of the HLA-B*2705 immune control of HIV, we first characterized the CD8 + T-cell responses of nine highly active antiretroviral therapy (HAART)-naïve B*2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B*2705-restricted Pol epitope, KRKGGIGGY (KY9), in 8/9 subjects. The magnitude of the KY9 response was only marginally lower than that of the KK10-specific response (median, 695 versus 867 spot-forming cells [SFC]/million peripheral blood mononuclear cells [PBMCs]; not significant [NS]), and viral escape mutants were observed in both KY9 and KK10, resulting from selection pressure driven by the respective CD8+ T-cell response. By comparing inhibitions of viral replication by CD8+ T cells specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B*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 h of infection, by KK10-and KY9-specific CD8+ T cells but not until 18 h postinfection by VL9-specific CD8+ T cells. There was no association between antiviral efficacy and proliferative capacity, cytotoxicity, polyfunctionality, or T-cell receptor (TCR) avidity. These data are consistent with previous studies indicating an important role for the B*2705-Gag KK10 response in the control of HIV but also suggest a previously unrecognized role played by the subdominant Pol-specific KY9 response in HLA-B*2705-mediated control of HIV and that the 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. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Payne, Rebecca P.
United Kingdom, Oxford
Nuffield Department of Medicine
Kløverpris, Henrik N.
United Kingdom, Oxford
Nuffield Department of Medicine
Sacha, Jonah B.
United States, Madison
University of Wisconsin-madison
Brumme, Zabrina L.
Canada, Burnaby
Simon Fraser University
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Brumme, Chanson J.
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Buus, Soren
Denmark, Copenhagen
Københavns Universitet
Sims, Stuart
United Kingdom, Oxford
Nuffield Department of Medicine
Hickling, Stephen
United Kingdom, Oxford
Nuffield Department of Medicine
United Kingdom, Oxford
University of Oxford
Riddell, Lynn A.
United Kingdom, Northampton
Northampton Healthcare Nhs Foundation Trust
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Nhs Foundation Trust
Luzzi, Graz A.
United Kingdom, High Wycombe
Wycombe Hospital
Edwards, Anne R.
United Kingdom, Oxford
Churchill Hospital
Phillips, Rodney E.
United Kingdom, Oxford
Nuffield Department of Medicine
Prado, Julia Garcia
United Kingdom, Oxford
Nuffield Department of Medicine
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
Nuffield Department of Medicine
United States, Boston
Massachusetts General Hospital
South Africa, Durban
University of Kwazulu-natal
Statistics
Citations: 94
Authors: 15
Affiliations: 13
Identifiers
Doi:
10.1128/JVI.00793-10
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases