title: Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells.
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.
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ternette
authors.affiliation: NIHR Oxford Biomedical Research Centre, Oxford, UK.|Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Yang
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Partridge
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Anuska
authors.initials: A
authors.lastname: Llano
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona, Badalona, Spain.
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeño
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Roman
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Charles
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Nadine L
authors.initials: NL
authors.lastname: Dudek
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona, Badalona, Spain.|Lluita contra la Sida' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain.|Universitat de Vic - Universitat Central de Catalunya, Vic, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.affiliation: HIV Unit, Hospital de la Vall d'Hebrón, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Crespo
authors.affiliation: Group T-6, Theoretical Biology, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Fischer
authors.affiliation: Group T-6, Theoretical Biology, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Bette T M
authors.initials: BT
authors.lastname: Korber
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.affiliation: HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona, Badalona, Spain.|Universitat de Vic - Universitat Central de Catalunya, Vic, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|NIHR Oxford Biomedical Research Centre, Oxford, UK.|Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D053719:Tandem Mass Spectrometry
chemical_list: D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I
keywords: Cytotoxic T cells; Human immunodeficiency virus type I; Human leukocyte antigen; Immunopeptidome; Mass spectrometry