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High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted gag-derived epitopes associated with relative HIV control

Berger, Christoph T., Frahm, Nicole, Price, David, Mothe, Beatriz, Ghebremichael, Musie, Hartman, Kari L., Henry, Leah M., Brenchley, Jason M., Ruff, Laura E., Venturi, Vanessa, Pereyra, Florencia, Sidney, John, Sette, Alessandro, Douek, Daniel C., Walker, Bruce D., Kaufmann, Daniel E. and Brander, Christian 2011. High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted gag-derived epitopes associated with relative HIV control. Journal of Virology 85 (18) , pp. 9334-9345. 10.1128/JVI.00460-11

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Abstract

Virus-specific cytotoxic T lymphocytes (CTL) with high levels of functional avidity have been associated with viral clearance in hepatitis C virus infection and enhanced antiviral protective immunity in animal models. However, the role of functional avidity as a determinant of HIV-specific CTL efficacy remains to be assessed. Here, we measured the functional avidities of HIV-specific CTL responses targeting 20 different, optimally defined CTL epitopes restricted by 13 different HLA class I alleles in a cohort comprising 44 HIV controllers and 68 HIV non-controllers. Responses restricted by HLA-B alleles and responses targeting epitopes located in HIV Gag exhibited significantly higher functional avidities than responses restricted by HLA-A or HLA-C molecules (p=0.0003) or responses targeting epitopes outside Gag (p<0.0001). The functional avidities of Gag-specific and HLA-B-restricted responses were higher in HIV controllers than non-controllers (p=0.014 and p=0.018) and were not restored in HIV non-controllers initiating antiretroviral therapy. T-cell receptor (TCR) analyses revealed narrower TCR repertoires in higher avidity CTL populations, which were dominated by public TCR sequences in HIV controllers. Together, these data link the presence of high avidity Gag-specific and HLA-B-restricted CTL responses with viral suppression in vivo and provide new insights into the immune parameters that mediate spontaneous control of HIV infection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014)
Publisher: American Society for Microbiology
ISSN: 0022-538X
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 03:49
URI: http://orca.cf.ac.uk/id/eprint/27446

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