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

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; COVID-19 Genomics UK (COG-UK) Consortium; Mala K. Maini; Graham Ogg; Julian C. Knight; ISARIC4C Investigators; Yanchun Peng; Sarah L. Rowland-Jones; Tao Dong

doi:10.1016/j.isci.2021.103353

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

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, COVID-19 Genomics UK (COG-UK) Consortium, Mala K. Maini, Graham Ogg, Julian C. KnightISARIC4C Investigators, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong

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

56 Citations (Scopus)

9 Downloads (Pure)

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
DOIs	https://doi.org/10.1016/j.isci.2021.103353
Publication status	Published - 19 Nov 2021

Keywords

Immune response
Immunology
Molecular biology
Phylogenetics
Virology

Access to Document

10.1016/j.isci.2021.103353Licence: CC BY

PIIS2589004221013225Final published version, 2.03 MBLicence: CC BY

Cite this

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., COVID-19 Genomics UK (COG-UK) Consortium, Maini, M. K., Ogg, G., ... Dong, T. (2021). The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24(11), [103353]. https://doi.org/10.1016/j.isci.2021.103353

@article{83ea79fd57de44438f137477f79d3907,

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 = "{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 Alp Aydin and Baker, {David J.} and Themoula Charalampous and Lindsay Coupland and Davidson, {Rose K.} and Samir Dervisevic and Ebenezer Foster-Nyarko and Christopher Jeanes and Jones, {Christopher R.} and David Lee and Mather, {Alison E.} and Catherine Moore and Justin O'Grady and Page, {Andrew J.} and Prosolek, {Sophie J.} and Steven Rudder and Smith, {Kim S.} and Spurgin, {Lewis G.} and Rachael Stanley and Sarah Cole and Jones, {Christopher R.} and Hannah Massey and Dhiraj Ail and Gouri Koduri and David Price and Aarti Shah and Richard Smith and {COVID-19 Genomics UK (COG-UK) Consortium} and Maini, {Mala K.} and Graham Ogg and Knight, {Julian C.} and {ISARIC4C Investigators} and Yanchun Peng and Rowland-Jones, {Sarah L.} and Tao Dong",

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. ",

year = "2021",

month = nov,

day = "19",

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

language = "English",

volume = "24",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "11",

}

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, COVID-19 Genomics UK (COG-UK) Consortium, Maini, MK, Ogg, G, Knight, JC, ISARIC4C Investigators, Peng, Y, Rowland-Jones, SL & Dong, T 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 - 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 - Aydin, Alp

AU - Baker, David J.

AU - Charalampous, Themoula

AU - Coupland, Lindsay

AU - Davidson, Rose K.

AU - Dervisevic, Samir

AU - Foster-Nyarko, Ebenezer

AU - Jeanes, Christopher

AU - Jones, Christopher R.

AU - Lee, David

AU - Mather, Alison E.

AU - Moore, Catherine

AU - O'Grady, Justin

AU - Page, Andrew J.

AU - Prosolek, Sophie J.

AU - Rudder, Steven

AU - Smith, Kim S.

AU - Spurgin, Lewis G.

AU - Stanley, Rachael

AU - Cole, Sarah

AU - Jones, Christopher R.

AU - Massey, Hannah

AU - Ail, Dhiraj

AU - Koduri, Gouri

AU - Price, David

AU - Shah, Aarti

AU - Smith, Richard

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

AU - Maini, Mala K.

AU - Ogg, Graham

AU - Knight, Julian C.

AU - ISARIC4C Investigators

AU - Peng, Yanchun

AU - Rowland-Jones, Sarah L.

AU - Dong, Tao

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.

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

UR - http://www.scopus.com/inward/record.url?scp=85118773166&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2021.103353

DO - 10.1016/j.isci.2021.103353

M3 - Article

AN - SCOPUS:85118773166

VL - 24

JO - iScience

JF - iScience

SN - 2589-0042

IS - 11

M1 - 103353

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Cite this