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Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors
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Szomolay, Barbara, Liu, Jie, Brown, Paul E., Miles, John J., Clement, Mathew, Llewellyn-Lacey, Sian, Dolton, Garry, Ekeruche-Makinde, Julia, Lissina, Anya, Schauenburg, Andrea J., Sewell, Andrew K., Burrows, Scott R., Roederer, Mario, Price, David A., Wooldridge, Linda and Berg, Hugo van den (2016) Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors. Immunology and Cell Biology, 94 . pp. 573-582. doi:10.1038/icb.2016.12 ISSN 0818-9641.
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Official URL: http://dx.doi.org/10.1038/icb.2016.12
Abstract
Evidence indicates that autoimmunity can be triggered by virus-specific CD8+ T cells that crossreact with self-derived peptide epitopes presented on the cell surface by major histocompatibility complex class I (MHCI) molecules. Identification of the associated viral pathogens is challenging because individual T-cell receptors can potentially recognize up to a million different peptides. Here, we generate peptide length-matched combinatorial peptide library (CPL) scan data for a panel of virus-specific CD8+ T-cell clones spanning different restriction elements and a range of epitope lengths. CPL scan data drove a protein database search limited to viruses that infect humans. Peptide sequences were ranked in order of likelihood of recognition. For all anti-viral CD8+ T-cell clones examined in this study, the index peptide was either the top-ranked sequence or ranked as one of the most likely sequences to be recognized. Thus, we demonstrate that anti-viral CD8+ T-cell clones are highly focused on their index peptide sequence and that ‘CPL-driven database searching’ can be used to identify the inciting virus-derived epitope for a given CD8+ T-cell clone. Moreover, to augment access to CPL-driven database searching, we have created a publicly accessible webtool. Application of these methodologies in the clinical setting may clarify the role of viral pathogens in the etiology of autoimmune diseases.
Item Type: | Journal Article | ||||||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR355 Virology |
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Divisions: | Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre | ||||||||||
Library of Congress Subject Headings (LCSH): | Viruses, Autoimmunity, Peptides, Antigenic determinants, Database searching | ||||||||||
Journal or Publication Title: | Immunology and Cell Biology | ||||||||||
Publisher: | Nature Publishing Group | ||||||||||
ISSN: | 0818-9641 | ||||||||||
Official Date: | 2016 | ||||||||||
Dates: |
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Volume: | 94 | ||||||||||
Page Range: | pp. 573-582 | ||||||||||
DOI: | 10.1038/icb.2016.12 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
Date of first compliant deposit: | 23 June 2016 | ||||||||||
Date of first compliant Open Access: | 23 June 2016 | ||||||||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England) | ||||||||||
Grant number: | Grant BB/H001085/1 (BBSRC), WT079848MA (Wellcome Trust) |
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