Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells

Nicola Ternette, Hongbing Yang, Thomas Partridge, Anuska Llano, Samandhy Cedeño, Roman Fischer, Philip D. Charles, Nadine L. Dudek, Beatriz Mothe, Manuel Crespo, William M. Fischer, Bette T. M. Korber, Morten Nielsen, Persephone Borrow, Anthony W. Purcell, Christian Brander, Lucy Dorrell, Benedikt M. Kessler, Tomáš Hanke

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    Abstract

    Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T-cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4+ T cells and the C8166 human T-cell line. Importantly, one-third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82% of the identified sequences originated from viral protein regions for which T-cell responses have previously been reported but for which the precise HLA class I-binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T-cell vaccine development.
    Original languageEnglish
    JournalEuropean Journal of Immunology
    Volume46
    Issue number1
    Pages (from-to)60-69
    Number of pages10
    ISSN0014-2980
    DOIs
    Publication statusPublished - 2016

    Bibliographical note

    © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Keywords

    • Cytotoxic T cells
    • Human immunodeficiency virus type I
    • Human leukocyte antigen
    • Immunopeptidome
    • Mass spectrometry

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