@article{63775bcd3992449f8da9368a19919a39,
title = "HLA-B*14:02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection",
abstract = "Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.",
keywords = "CD8 T cells, HIV, HLA-B*14, Immune control",
author = "Leitman, {Ellen M.} and Willberg, {Christian B.} and Tsai, {Ming Han} and Huabiao Chen and S{\o}ren Buus and Fabian Chen and Lynn Riddell and David Haas and Jacques Fellay and Goedert, {James J.} and Alicja Piechocka-Trocha and Walker, {Bruce D.} and Jeffrey Martin and Steven Deeks and Wolinsky, {Steven M.} and Jeremy Martinson and Maureen Martin and Ying Qi and Asier S{\'a}ez-Ciri{\'o}n and Yang, {Otto O.} and Matthews, {Philippa C.} and Mary Carrington and Goulder, {Philip J.R.}",
note = "Funding Information: This work was funded by grants from the National Institutes of Health (RO1AI46995 to P.J.R.G.), the Wellcome Trust (WT104748MA to P.J.R.G.), NIHR research capability funding (to P.C.M.), and the Clarendon Fund (to E.M.L.). This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under contract no. HHSN261200800001E (to M.C.). The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), U01-AI35042 (Johns Hopkins University Bloomberg School of Public Health, Joseph Margolick, principal investigator [PI]), U01-AI35039 (Northwestern University, Steven Wolinsky, PI), U01-AI35040 (University of California, Los Angeles, Roger Detels and Oto Martinez, MPI), U01-AI35041 (University of Pittsburgh, Charles Rinaldo, PI), and UM1-AI35043 (Johns Hopkins University Bloomberg School of Public Health, Lisa Jacobson, PI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: CD3.4 bispecific monoclonal antibody (catalog no. 12278), from Johnson Wong and Galit Alter. The authors have declared that no competing interests exist. Publisher Copyright: {\textcopyright} 2017 American Society for Microbiology.",
year = "2017",
month = nov,
day = "1",
doi = "10.1128/JVI.00544-17",
language = "English (US)",
volume = "91",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "22",
}
