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

COVID-19 Genomics UK (COG-UK) Consortium; ISARIC4C Investigators; Thushan I. de Silva; Guihai Liu; Benjamin B. Lindsey; Danning Dong; Shona C. Moore; Nienyun Sharon Hsu; Dhruv Shah; Dannielle Wellington; Alexander J. Mentzer; Adrienn Angyal; Rebecca Brown; Matthew D. Parker; Zixi Ying; Xuan Yao; Lance Turtle; Susanna Dunachie

doi:10.1016/j.isci.2021.103353

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

COVID-19 Genomics UK (COG-UK) Consortium
, ISARIC4C Investigators
, Thushan I. de Silva
, Guihai Liu
, Benjamin B. Lindsey
, Danning Dong
, Shona C. Moore
, Nienyun Sharon Hsu
, Dhruv Shah
, Dannielle Wellington
, Alexander J. Mentzer
, Adrienn Angyal
, Rebecca Brown
, Matthew D. Parker
, Zixi Ying
, Xuan Yao
, Lance Turtle
, Susanna Dunachie

https://isaric4c.net
University of Sheffield
London School of Hygiene and Tropical Medicine
University of Oxford
Capital Medical University
Xinjiang Medical University
University of Liverpool
Liverpool University Hospitals NHS Foundation Trust
Mahidol University
University of Nottingham

Research output: Contribution to journal › Article › peer-review

76 Citations (Scopus)

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.

Original language	English
Article number	103353
Journal	iScience
Volume	24
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2021.103353
Publication status	Published - 19 Nov 2021

Keywords

Immune response
Immunology
Molecular biology
Phylogenetics
Virology

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COVID-19 Genomics UK (COG-UK) Consortium, ISARIC4C Investigators, de Silva, T. I., Liu, G., Lindsey, B. B., Dong, D., Moore, S. C., Hsu, N. S., Shah, D., Wellington, D., Mentzer, A. J., Angyal, A., Brown, R., Parker, M. D., Ying, Z., Yao, X., Turtle, L., & Dunachie, S. (2021). The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24(11), Article 103353. https://doi.org/10.1016/j.isci.2021.103353

@article{31afa7b356b142738ee400a1b4dc227e,

title = "The impact of viral mutations on recognition by SARS-CoV-2 specific T cells",

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.",

keywords = "Immune response, Immunology, Molecular biology, Phylogenetics, Virology",

author = "\{COVID-19 Genomics UK (COG-UK) Consortium\} and \{ISARIC4C Investigators\} and \{de Silva\}, \{Thushan I.\} and Guihai Liu and Lindsey, \{Benjamin B.\} and Danning Dong and Moore, \{Shona C.\} and Hsu, \{Nienyun Sharon\} and Dhruv Shah and Dannielle Wellington and Mentzer, \{Alexander J.\} and Adrienn Angyal and Rebecca Brown and Parker, \{Matthew D.\} and Zixi Ying and Xuan Yao and Lance Turtle and Susanna Dunachie and Aanensen, \{David M.\} and Khalil Abudahab and Helen Adams and Alexander Adams and Safiah Afifi and Dinesh Aggarwal and Ahmad, \{Shazaad S.Y.\} and Louise Aigrain and Adela Alcolea-Medina and Alikhan, \{Nabil Fareed\} and Elias Allara and Roberto Amato and Tara Annett and Stephen Aplin and Ariani, \{Cristina V.\} and Hibo Asad and Amy Ash and Paula Ashfield and Fiona Ashford and Laura Atkinson and Attwood, \{Stephen W.\} and Cressida Auckland and Alp Aydin and Baker, \{David J.\} and Paul Baker and Balcazar, \{Carlos E.\} and Jonathan Ball and Barrett, \{Jeffrey C.\} and Magdalena Barrow and Edward Barton and Matthew Bashton and Bassett, \{Andrew R.\} and Sally Forrest and Lorna Finch",

year = "2021",

month = nov,

day = "19",

doi = "10.1016/j.isci.2021.103353",

language = "English",

volume = "24",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "11",

}

COVID-19 Genomics UK (COG-UK) Consortium, ISARIC4C Investigators, de Silva, TI, Liu, G, Lindsey, BB, Dong, D, Moore, SC, Hsu, NS, Shah, D, Wellington, D, Mentzer, AJ, Angyal, A, Brown, R, Parker, MD, Ying, Z, Yao, X, Turtle, L & Dunachie, S 2021, 'The impact of viral mutations on recognition by SARS-CoV-2 specific T cells', iScience, vol. 24, no. 11, 103353. https://doi.org/10.1016/j.isci.2021.103353

TY - JOUR

T1 - The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

AU - COVID-19 Genomics UK (COG-UK) Consortium

AU - ISARIC4C Investigators

AU - de Silva, Thushan I.

AU - Liu, Guihai

AU - Lindsey, Benjamin B.

AU - Dong, Danning

AU - Moore, Shona C.

AU - Hsu, Nienyun Sharon

AU - Shah, Dhruv

AU - Wellington, Dannielle

AU - Mentzer, Alexander J.

AU - Angyal, Adrienn

AU - Brown, Rebecca

AU - Parker, Matthew D.

AU - Ying, Zixi

AU - Yao, Xuan

AU - Turtle, Lance

AU - Dunachie, Susanna

AU - Aanensen, David M.

AU - Abudahab, Khalil

AU - Adams, Helen

AU - Adams, Alexander

AU - Afifi, Safiah

AU - Aggarwal, Dinesh

AU - Ahmad, Shazaad S.Y.

AU - Aigrain, Louise

AU - Alcolea-Medina, Adela

AU - Alikhan, Nabil Fareed

AU - Allara, Elias

AU - Amato, Roberto

AU - Annett, Tara

AU - Aplin, Stephen

AU - Ariani, Cristina V.

AU - Asad, Hibo

AU - Ash, Amy

AU - Ashfield, Paula

AU - Ashford, Fiona

AU - Atkinson, Laura

AU - Attwood, Stephen W.

AU - Auckland, Cressida

AU - Aydin, Alp

AU - Baker, David J.

AU - Baker, Paul

AU - Balcazar, Carlos E.

AU - Ball, Jonathan

AU - Barrett, Jeffrey C.

AU - Barrow, Magdalena

AU - Barton, Edward

AU - Bashton, Matthew

AU - Bassett, Andrew R.

AU - Forrest, Sally

AU - Finch, Lorna

PY - 2021/11/19

Y1 - 2021/11/19

N2 - 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.

AB - 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.

KW - Immune response

KW - Immunology

KW - Molecular biology

KW - Phylogenetics

KW - Virology

U2 - 10.1016/j.isci.2021.103353

DO - 10.1016/j.isci.2021.103353

M3 - Article

SN - 2589-0042

VL - 24

JO - iScience

JF - iScience

IS - 11

M1 - 103353

ER -

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

Abstract

Keywords

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