|
|||||
|
|
Defining the HLA class I‐associated viral antigen repertoire from HIV‐1‐infected human cells |
|
| Authors: | 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 |
| Affiliation: | 1. The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK;2. Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK;3. NIHR Oxford Biomedical Research Centre, Oxford, UK;4. Nuffield Department of Medicine, University of Oxford, Oxford, UK;5. HIVACAT, Irsicaixa AIDS Research Institute, Autonomous University of Barcelona, Badalona, Spain;6. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia;7. Lluita contra la Sida’ Foundation, Hospital Germans Trias i Pujol, Badalona, Spain;8. Universitat de Vic – Universitat Central de Catalunya, Vic, Spain;9. HIV Unit, Hospital de la Vall d'Hebrón, Barcelona, Spain;10. Group T‐6, Theoretical Biology, Los Alamos National Laboratory, Los Alamos, NM, USA;11. Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark;12. Institució Catalana de Recerca i Estudis Avan?ats (ICREA), Barcelona, Spain |
| 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. |
| Keywords: | Cytotoxic T cells Human immunodeficiency virus type I Human leukocyte antigen Immunopeptidome Mass spectrometry |