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; Dinesh Aggarwal; Shazaad S.Y. Ahmad; David Bibby; Vicki Chalker; Meera Chand; Gavin Dabrera; Nicholas Ellaby; Eileen Gallagher; Ian Harrison; Miren Iturriza-Gomara; Stephen P. Kidd; Angie Lackenby; Nicholas J. Loman; Nicholas W. Machin; Caoimhe McKerr; Richard Myers; Surendra Parmar; Sharon J. Peacock; Katherine A. Twohig; Anthony P. Underwood; Jake Dunning; Richard S. Tedder; Maria Zambon

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, Dinesh Aggarwal, Shazaad S.Y. AhmadDavid Bibby, Vicki Chalker, Meera Chand, Gavin Dabrera, Nicholas Ellaby, Eileen Gallagher, Ian Harrison, Miren Iturriza-Gomara, Stephen P. Kidd, Angie Lackenby, Nicholas J. Loman, Nicholas W. Machin, Caoimhe McKerr, Richard Myers, Surendra Parmar, Sharon J. Peacock, Katherine A. Twohig, Anthony P. Underwood, Jake Dunning, Richard S. Tedder, Maria Zambon

^*Corresponding author for this work

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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 FTSDYYQLY_207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF_9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK_361-369. 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
Early online date	28 Oct 2021
DOIs	https://doi.org/10.1016/j.isci.2021.103353
Publication status	Published - 19 Nov 2021

Bibliographical note

Funding Information: This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, and UK Research and Innovation (UKRI)/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data was undertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust (grant number 205228/Z/16/Z) and by the University of Liverpool Centre for Excellence in Infectious Disease Research (CEIDR). S.D. is funded by an NIHR Global Research Professorship (NIHR300791). L.T. and S.C.M. are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical Research Centre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Publisher Copyright: © 2021 The Author(s).

Citation: Thushan I. de Silva et al The impact of viral mutations on recognition by SARS-CoV-2 specific T cells, iScience, Volume 24, Issue 11, 2021, 103353, ISSN 2589-0042,

DOI: https://doi.org/10.1016/j.isci.2021.103353.

Keywords

Immune response
Immunology
Molecular biology
Phylogenetics
Virology

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deSilva2021The ImpactOfViralMutationsOnRecognitioniScienceFinal published version, 2.03 MBLicence: CC BY

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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., Aggarwal, D., ... Zambon, M. (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

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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.",

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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 David Bibby and Vicki Chalker and Meera Chand and Gavin Dabrera and Nicholas Ellaby and Eileen Gallagher and Ian Harrison and Miren Iturriza-Gomara and Kidd, {Stephen P.} and Angie Lackenby and Loman, {Nicholas J.} and Machin, {Nicholas W.} and Caoimhe McKerr and Richard Myers and Surendra Parmar and Peacock, {Sharon J.} and Twohig, {Katherine A.} and Underwood, {Anthony P.} and Jake Dunning and Tedder, {Richard S.} and Maria Zambon",

note = "Funding Information: This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, and UK Research and Innovation (UKRI)/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data was undertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust (grant number 205228/Z/16/Z) and by the University of Liverpool Centre for Excellence in Infectious Disease Research (CEIDR). S.D. is funded by an NIHR Global Research Professorship (NIHR300791). L.T. and S.C.M. are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical Research Centre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Publisher Copyright: {\textcopyright} 2021 The Author(s). Citation: Thushan I. de Silva et al The impact of viral mutations on recognition by SARS-CoV-2 specific T cells, iScience, Volume 24, Issue 11, 2021, 103353, ISSN 2589-0042, DOI: https://doi.org/10.1016/j.isci.2021.103353.",

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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, Aggarwal, D, Ahmad, SSY , Bibby, D, Chalker, V, Chand, M , Dabrera, G, Ellaby, N, Gallagher, E, Harrison, I, Iturriza-Gomara, M, Kidd, SP, Lackenby, A, Loman, NJ, Machin, NW, McKerr, C, Myers, R, Parmar, S, Peacock, SJ, Twohig, KA, Underwood, AP, Dunning, J, Tedder, RS & Zambon, M 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 - Bibby, David

AU - Chalker, Vicki

AU - Chand, Meera

AU - Dabrera, Gavin

AU - Ellaby, Nicholas

AU - Gallagher, Eileen

AU - Harrison, Ian

AU - Iturriza-Gomara, Miren

AU - Kidd, Stephen P.

AU - Lackenby, Angie

AU - Loman, Nicholas J.

AU - Machin, Nicholas W.

AU - McKerr, Caoimhe

AU - Myers, Richard

AU - Parmar, Surendra

AU - Peacock, Sharon J.

AU - Twohig, Katherine A.

AU - Underwood, Anthony P.

AU - Dunning, Jake

AU - Tedder, Richard S.

AU - Zambon, Maria

N1 - Funding Information: This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, and UK Research and Innovation (UKRI)/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data was undertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust (grant number 205228/Z/16/Z) and by the University of Liverpool Centre for Excellence in Infectious Disease Research (CEIDR). S.D. is funded by an NIHR Global Research Professorship (NIHR300791). L.T. and S.C.M. are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical Research Centre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Publisher Copyright: © 2021 The Author(s). Citation: Thushan I. de Silva et al The impact of viral mutations on recognition by SARS-CoV-2 specific T cells, iScience, Volume 24, Issue 11, 2021, 103353, ISSN 2589-0042, DOI: https://doi.org/10.1016/j.isci.2021.103353.

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

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U2 - 10.1016/j.isci.2021.103353

DO - 10.1016/j.isci.2021.103353

M3 - Article

AN - SCOPUS:85118773166

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

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