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...

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Detalles Bibliográficos
Autores: Ternette, Nicola, Yang, Hongbing, Partridge, Thomas, Llano Montero, Anuska|||0000-0002-0133-9888, Cedeño, Samandhy|||0000-0001-8312-0208, Fischer, Roman, Charles, Philip D., Dudek, Nadine L., Mothe, Beatriz|||0000-0001-9975-407X, Crespo Casal, Manuel|||0000-0001-9016-0515, Fischer, William M., Korber, Bette T. M., Nielsen, Morten, Borrow, Persephone, Purcell, Anthony W., Brander, Christian|||0000-0002-0548-5778, Dorrell, Lucy, Kessler, Benedikt M., Hanke, Tomáš|||0000-0002-6076-9546
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:185445
Acceso en línea:https://ddd.uab.cat/record/185445
https://dx.doi.org/urn:doi:10.1002/eji.201545890
Access Level:acceso abierto
Palabra clave:Cytotoxic T cells
Human immunodeficiency virus type I
Human leukocyte antigen
Immunopeptidome
Mass spectrometry
Descripción
Sumario: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.