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Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors

Szomolay, Barbara ORCID:, Liu, Jie, Brown, Paul E., Miles, John J., Clement, Mathew ORCID:, Llewellyn-Lacey, Sian, Dolton, Garry, Ekeruche-Makinde, Julia, Lissina, Anya, Schauenburg, Andrea J., Sewell, Andrew K. ORCID:, Burrows, Scott R., Roederer, Mario, Price, David A. ORCID:, Wooldridge, Linda and van den Berg, Hugo A. 2016. Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors. Immunology and Cell Biology 94 (6) , pp. 573-582. 10.1038/icb.2016.12

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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: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher: Nature Publishing Group
ISSN: 0818-9641
Date of First Compliant Deposit: 15 February 2017
Date of Acceptance: 18 January 2016
Last Modified: 19 Nov 2023 15:55

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