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Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses

Tan, CCS; Owen, CJ; Tham, CYL; Bertoletti, A; van Dorp, L; Balloux, F; (2021) Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses. Infection, Genetics and Evolution , 95 , Article 105075. 10.1016/j.meegid.2021.105075. Green open access

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Abstract

T-cell-mediated immunity to SARS-CoV-2-derived peptides in individuals unexposed to SARS-CoV-2 has been previously reported. This pre-existing immunity was suggested to largely derive from prior exposure to ‘common cold’ endemic human coronaviruses (HCoVs). To test this, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the full proteome of the Coronaviridae family. 54.8% of these epitopes had no homology to any of the HCoVs. Further, the proportion of SARS-CoV-2-derived epitopes with any level of sequence homology to the proteins encoded by any of the coronaviruses tested is well-predicted by their alignment-free phylogenetic distance to SARS-CoV-2 (Pearson's r = −0.958). No coronavirus in our dataset showed a significant excess of T-cell epitope homology relative to the proportion of expected random matches, given their genetic similarity to SARS-CoV-2. Our findings suggest that prior exposure to human or animal-associated coronaviruses cannot completely explain the T-cell repertoire in unexposed individuals that recognise SARS-CoV-2 cross-reactive epitopes.

Type: Article
Title: Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.meegid.2021.105075
Publisher version: https://doi.org/10.1016/j.meegid.2021.105075
Language: English
Additional information: © 2021 The Authors. Published by Elsevier B.V. under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10135160
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