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The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

2589-0042
103353
de Silva, Thushan I
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Liu, Guihai
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Lindsey, Benjamin B
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Dong, Danning
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Moore, Shona C
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Hsu, Nienyun Sharon
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Shah, Dhruv
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Wellington, Dannielle
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Mentzer, Alexander J
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Angyal, Adrienn
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Brown, Rebecca
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Parker, Matthew D
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Ying, Zixi
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Yao, Xuan
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Turtle, Lance
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Dunachie, Susanna
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Maini, Mala K
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Ogg, Graham
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Knight, Julian C
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Peng, Yanchun
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Rowland-Jones, Sarah L
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Dong, Tao
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Saeed, Kordo
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Dushianthan, Ahilanandan
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COVID-19 Genomics UK (COG-UK) consortium
de Silva, Thushan I
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Liu, Guihai
22b88f9f-450b-4691-bfcf-8b3c3d44e97f
Lindsey, Benjamin B
006d4ed8-212b-4913-9d4f-a1f957949cfa
Dong, Danning
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Moore, Shona C
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Hsu, Nienyun Sharon
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Shah, Dhruv
c78c3f32-5c3f-4d95-bbcd-4cf69a35559f
Wellington, Dannielle
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Mentzer, Alexander J
572ec0ac-39fd-415b-9779-ba6e7d5489ce
Angyal, Adrienn
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Brown, Rebecca
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Parker, Matthew D
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Ying, Zixi
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Yao, Xuan
2d675af3-85a2-40f6-9ab0-938dc1b4cfca
Turtle, Lance
46a79918-7fd1-4002-84d5-bc3bd0b26632
Dunachie, Susanna
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Maini, Mala K
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Ogg, Graham
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Knight, Julian C
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Peng, Yanchun
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Rowland-Jones, Sarah L
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Dong, Tao
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Saeed, Kordo
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Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751

de Silva, Thushan I, Liu, Guihai, Lindsey, Benjamin B, Moore, Shona C, Hsu, Nienyun Sharon, Shah, Dhruv, Wellington, Dannielle, Mentzer, Alexander J, Angyal, Adrienn, Parker, Matthew D, Ying, Zixi, Yao, Xuan, Turtle, Lance, Dunachie, Susanna and Dushianthan, Ahilanandan , COVID-19 Genomics UK (COG-UK) consortium (2021) The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24 (11), 103353. (doi:10.1016/j.isci.2021.103353).

Record type: Article

Abstract

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

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Published date: 19 November 2021

Identifiers

Local EPrints ID: 455680
URI: http://eprints.soton.ac.uk/id/eprint/455680
DOI: doi:10.1016/j.isci.2021.103353
ISSN: 2589-0042
PURE UUID: d9f33d18-612e-4ae9-a931-28058d614a23
ORCID for Kordo Saeed: ORCID iD orcid.org/0000-0003-0123-0302
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359

Catalogue record

Date deposited: 30 Mar 2022 16:48
Last modified: 08 Oct 2024 01:59

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Contributors

Author: Thushan I de Silva
Author: Guihai Liu
Author: Benjamin B Lindsey
Author: Danning Dong
Author: Shona C Moore
Author: Nienyun Sharon Hsu
Author: Dhruv Shah
Author: Dannielle Wellington
Author: Alexander J Mentzer
Author: Adrienn Angyal
Author: Rebecca Brown
Author: Matthew D Parker
Author: Zixi Ying
Author: Xuan Yao
Author: Lance Turtle
Author: Susanna Dunachie
Author: Mala K Maini
Author: Graham Ogg
Author: Julian C Knight
Author: Yanchun Peng
Author: Sarah L Rowland-Jones
Author: Tao Dong
Author: Kordo Saeed ORCID iD
Author: Ahilanandan Dushianthan ORCID iD
Corporate Author: COVID-19 Genomics UK (COG-UK) consortium

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