Identification of CD8+ T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL |
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| Authors: | Mette Voldby Larsen Alina Lelic Robin Parsons Morten Nielsen Ilka Hoof Kasper Lamberth Mark B Loeb S?ren Buus Jonathan Bramson Ole Lund |
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| Institution: | 1. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.; 2. Department of Pathology and Molecular Medicine, Institute for Molecular Medicine and Health, McMaster University, Hamilton, Ontario, Canada.; 3. Division of Experimental Immunology, Institute of Medical Microbiology and Immunology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.;New York University, United States of America |
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| Abstract: | BackgroundWest Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies.Methodology/Principal FindingsIn a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8+ T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8+ T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World.Conclusions/SignificanceThe 26 identified CD8+ T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8+ T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine. |
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