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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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COVID-19 Genomics UK (COG-UK) consortium
de Silva, Thushan I
6b5b0a5a-31bb-4f59-a920-df219fdfe320
Liu, Guihai
22b88f9f-450b-4691-bfcf-8b3c3d44e97f
Lindsey, Benjamin B
006d4ed8-212b-4913-9d4f-a1f957949cfa
Dong, Danning
33dfcfb4-c3ae-47fc-b93b-d2e9ff920e07
Moore, Shona C
b2fd0970-e2be-4d9f-a31c-ed29cc8762b5
Hsu, Nienyun Sharon
1cf58394-c80e-4b9d-bc24-9ec550e9e7bf
Shah, Dhruv
c78c3f32-5c3f-4d95-bbcd-4cf69a35559f
Wellington, Dannielle
675931a2-122b-464c-9aff-9be9879580fc
Mentzer, Alexander J
572ec0ac-39fd-415b-9779-ba6e7d5489ce
Angyal, Adrienn
9e7d07dc-323c-468a-9c9d-a202b5c68f2a
Brown, Rebecca
2d9828f1-7cc4-4678-88f3-a0345c86ffb9
Parker, Matthew D
5b0008a7-ee6f-4f2f-a05e-f35f7bcf6c28
Ying, Zixi
c2925623-f2f1-48d3-8379-aee3895d98d5
Yao, Xuan
2d675af3-85a2-40f6-9ab0-938dc1b4cfca
Turtle, Lance
46a79918-7fd1-4002-84d5-bc3bd0b26632
Dunachie, Susanna
459078d4-daf0-4ba1-ab82-00da9d937bce
Maini, Mala K
4c93ff58-ca79-4489-8e1d-52b75f810b46
Ogg, Graham
6165bb98-ee4f-4533-8eda-0072a0a73be3
Knight, Julian C
5426d742-f8e7-420b-b0b1-f8bdf437f719
Peng, Yanchun
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Rowland-Jones, Sarah L
b3b72ad7-5884-4d80-9163-f4faa1075f34
Dong, Tao
942142fb-76a5-430c-85ae-17155db4263d
Saeed, Kordo
87cb67e5-71e8-4759-bf23-2ea00ebd8b39

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 and Dunachie, Susanna , 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

Catalogue record

Date deposited: 30 Mar 2022 16:48
Last modified: 10 Apr 2024 02:01

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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
Corporate Author: COVID-19 Genomics UK (COG-UK) consortium

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