dc.contributor.author | Berger, Christoph T. | |
dc.contributor.author | Frahm, Nicole | |
dc.contributor.author | Price, David A. | |
dc.contributor.author | Mothe, Beatriz | |
dc.contributor.author | Ghebremichael, Musie | |
dc.contributor.author | Hartman, Kari L. | |
dc.contributor.author | Henry, Leah M. | |
dc.contributor.author | Brenchley, Jason M. | |
dc.contributor.author | Ruff, Laura E. | |
dc.contributor.author | Venturi, Vanessa | |
dc.contributor.author | Pereyra, Florencia | |
dc.contributor.author | Sidney, John | |
dc.contributor.author | Sette, Alessandro | |
dc.contributor.author | Douek, Daniel C. | |
dc.contributor.author | Walker, Bruce D. | |
dc.contributor.author | Kaufmann, Daniel E. | |
dc.contributor.author | Brander, Christian | |
dc.date.accessioned | 2019-10-13T16:03:00Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Berger, C. T., N. Frahm, D. A. Price, B. Mothe, M. Ghebremichael, K. L. Hartman, L. M. Henry, et al. 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): 9334–45. doi:10.1128/JVI.00460-11. | |
dc.identifier.issn | 0022-538X | |
dc.identifier.issn | 1070-6321 | |
dc.identifier.issn | 1098-5514 | |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542772 | * |
dc.description.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 with 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 noncontrollers. 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 in noncontrollers (P = 0.014 and P = 0.018) and were not restored in HIV noncontrollers 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. | |
dc.language.iso | en_US | |
dc.publisher | American Society for Microbiology | |
dash.license | LAA | |
dc.title | High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control | |
dc.type | Journal Article | |
dc.description.version | Version of Record | |
dc.relation.journal | Journal of Virology | |
dash.depositing.author | Ghebremichael, Musie::d81cb6c53a9541ab3a5c0636793f27e9::600 | |
dc.date.available | 2019-10-13T16:03:00Z | |
dash.workflow.comments | 1Science Serial ID 65144 | |
dc.identifier.doi | 10.1128/JVI.00460-11 | |
dash.source.volume | 85;18 | |
dash.source.page | 9334 | |