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

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.Fil: Ternette, Nicola. University of Oxford; Reino UnidoFil: Yang, Hongbing. University of Oxford; Reino UnidoFil: Partridge, Thomas. University of Oxford; Reino UnidoFil: Llano, Anuska. Universitat Autònoma de Barcelona; EspañaFil: Cedeño, Samandhy. Universitat Autònoma de Barcelona; EspañaFil: Fischer, Roman. University of Oxford; Reino UnidoFil: Charles, Philip D.. University of Oxford; Reino UnidoFil: Dudek, Nadine L.. Monash University; AustraliaFil: Mothe, Beatriz. Hospital Universitari Germans Trias I Pujol; . Universitat Autònoma de Barcelona; España. Hospital Germans Trias i Pujol; EspañaFil: Crespo, Manuel. Universitat Central de Catalunya; España. Hospital de la Vall d'Hebrón. HIV Unit; EspañaFil: Fischer, William M.. Los Alamos National High Magnetic Field Laboratory; Estados UnidosFil: Korber, Bette T. M.. Los Alamos National High Magnetic Field Laboratory; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. Technical University of Denmark; DinamarcaFil: Borrow, Persephone. University of Oxford; Reino UnidoFil: Purcell, Anthony W.. Monash University; AustraliaFil: Brander, Christian. Universitat Autònoma de Barcelona; España. Institució Catalana de Recerca i Estudis Avancats; España. Universitat Central de Catalunya; EspañaFil: Dorrell, Lucy. University of Oxford; Reino UnidoFil: Kessler, Benedikt M.. University of Oxford; Reino UnidoFil: Hanke, Tomáš. University of Oxford; Reino Unid