RESEARCH ARTICLE
HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses Nathan Erdmann1, Victor Y. Du1, Jonathan Carlson2, Malinda Schaefer3, Alexander Jureka1, Sarah Sterrett1, Ling Yue3, Dario Dilernia3, Shabir Lakhi4, Jianming Tang1, John Sidney5, Jill Gilmour6, Susan Allen3, Eric Hunter3, Sonya Heath1, Anju Bansal1, Paul A. Goepfert1* 1 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Microsoft Research, Los Angeles, California, United States of America, 3 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America, 4 Zambia Emory Research Project, Lusaka, Zambia, 5 La Jolla Institute for Allergy & Immunology, La Jolla, California, United States of America, 6 International AIDS Vaccine Institute and Imperial College, London, United Kingdom *
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OPEN ACCESS Citation: Erdmann N, Du VY, Carlson J, Schaefer M, Jureka A, Sterrett S, et al. (2015) HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses. PLoS Pathog 11(8): e1005111. doi:10.1371/journal.ppat.1005111 Editor: Ronald Swanstrom, University of North Carolina at Chapel Hill, UNITED STATES Received: June 5, 2015 Accepted: July 27, 2015 Published: August 24, 2015 Copyright: © 2015 Erdmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by these NIH grants: 5R01AI084772-05, 1R01AI112566-01A1, and 5R01AI064060-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Jonathan Carlson is employed by Microsoft. This does not alter our adherence to all PLOS Pathogens policies on sharing data and
Abstract Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p
