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; David M. Aanensen; Khalil Abudahab; Helen Adams; Alexander Adams; Safiah Afifi; Dinesh Aggarwal; Shazaad S.Y. Ahmad; Louise Aigrain; Adela Alcolea-Medina; Chris Baxter; Declan T. Bradley; Stephen Bridgett; Anna Casey; Tanya Curran; Thomas Davis; Derek J. Fairley; Marc Fuchs; Salman Goudarzi; William L. Hamilton; David K. Jackson; Kate Johnson; Sophie Jones; Christopher R. Jones; Deborah Lavin; Jack Lee; Arun Mariappan; James P. McKenna; Julia Miskelly; Zoltan Molnar; Jonathan Moore; Catherine Moore; Leanne J. Murray; Darren R. Murray; Husam Osman; COVID-19 Genomics UK (COG-UK) Consortium

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, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander AdamsSafiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Chris Baxter, Declan T. Bradley, Stephen Bridgett, Anna Casey, Tanya Curran, Thomas Davis, Derek J. Fairley, Marc Fuchs, Salman Goudarzi, William L. Hamilton, David K. Jackson, Kate Johnson, Sophie Jones, Christopher R. Jones, Deborah Lavin, Jack Lee, Arun Mariappan, James P. McKenna, Julia Miskelly, Zoltan Molnar, Jonathan Moore, Catherine Moore, Leanne J. Murray, Darren R. Murray, Husam Osman, COVID-19 Genomics UK (COG-UK) Consortium

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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 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
Early online date	09 Nov 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.

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. T.I.d.S. and T.D. conceptualized the project; T.D. T.I.d.S. L.T. and Y.P. designed and supervised T cell experiments; B.B.L. N.S.H. and M.D.P. conducted the viral sequence analyses; D.S. conducted the literature review and collated T cell epitope information; G.L. D.D. and S.C.M. performed experiments and analyzed the data; X.Y. Z.Y. A.A. and R.B. provided critical reagents and technical assistance; J.C.K. and A.J.M. established clinical cohorts; T.I.d.S. and T.D. wrote and edited the original draft; all co-authors reviewed and edited the manuscript. The authors have no competing interests to declare.

Publisher Copyright:
© 2021 The Author(s)

Keywords

Immune response
Immunology
Molecular biology
Phylogenetics
Virology

ASJC Scopus subject areas

General

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The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
Copyright 2022 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
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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., Aanensen, D. M., Abudahab, K., Adams, H., ... 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), Article 103353. https://doi.org/10.1016/j.isci.2021.103353

@article{34895bfbcf904838a9ef7c903f07d5e2,

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 Louise Aigrain and Adela Alcolea-Medina and Chris Baxter and Bradley, {Declan T.} and Stephen Bridgett and Anna Casey and Tanya Curran and Thomas Davis and Fairley, {Derek J.} and Marc Fuchs and Salman Goudarzi and Hamilton, {William L.} and Jackson, {David K.} and Kate Johnson and Sophie Jones and Jones, {Christopher R.} and Deborah Lavin and Jack Lee and Arun Mariappan and McKenna, {James P.} and Julia Miskelly and Zoltan Molnar and Jonathan Moore and Catherine Moore and Murray, {Leanne J.} and Murray, {Darren R.} and Husam Osman and {COVID-19 Genomics UK (COG-UK) Consortium}",

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. 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. T.I.d.S. and T.D. conceptualized the project; T.D. T.I.d.S. L.T. and Y.P. designed and supervised T cell experiments; B.B.L. N.S.H. and M.D.P. conducted the viral sequence analyses; D.S. conducted the literature review and collated T cell epitope information; G.L. D.D. and S.C.M. performed experiments and analyzed the data; X.Y. Z.Y. A.A. and R.B. provided critical reagents and technical assistance; J.C.K. and A.J.M. established clinical cohorts; T.I.d.S. and T.D. wrote and edited the original draft; all co-authors reviewed and edited the manuscript. The authors have no competing interests to declare. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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",

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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, Aanensen, DM, Abudahab, K, Adams, H, Adams, A, Afifi, S, Aggarwal, D, Ahmad, SSY, Aigrain, L, Alcolea-Medina, A, Baxter, C, Bradley, DT, Bridgett, S , Casey, A, Curran, T, Davis, T, Fairley, DJ, Fuchs, M, Goudarzi, S, Hamilton, WL, Jackson, DK, Johnson, K, Jones, S, Jones, CR, Lavin, D, Lee, J, Mariappan, A, McKenna, JP, Miskelly, J, Molnar, Z, Moore, J, Moore, C, Murray, LJ , Murray, DR, Osman, H & COVID-19 Genomics UK (COG-UK) Consortium 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 - Aigrain, Louise

AU - Alcolea-Medina, Adela

AU - Baxter, Chris

AU - Bradley, Declan T.

AU - Bridgett, Stephen

AU - Casey, Anna

AU - Curran, Tanya

AU - Davis, Thomas

AU - Fairley, Derek J.

AU - Fuchs, Marc

AU - Goudarzi, Salman

AU - Hamilton, William L.

AU - Jackson, David K.

AU - Johnson, Kate

AU - Jones, Sophie

AU - Jones, Christopher R.

AU - Lavin, Deborah

AU - Lee, Jack

AU - Mariappan, Arun

AU - McKenna, James P.

AU - Miskelly, Julia

AU - Molnar, Zoltan

AU - Moore, Jonathan

AU - Moore, Catherine

AU - Murray, Leanne J.

AU - Murray, Darren R.

AU - Osman, Husam

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

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. 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. T.I.d.S. and T.D. conceptualized the project; T.D. T.I.d.S. L.T. and Y.P. designed and supervised T cell experiments; B.B.L. N.S.H. and M.D.P. conducted the viral sequence analyses; D.S. conducted the literature review and collated T cell epitope information; G.L. D.D. and S.C.M. performed experiments and analyzed the data; X.Y. Z.Y. A.A. and R.B. provided critical reagents and technical assistance; J.C.K. and A.J.M. established clinical cohorts; T.I.d.S. and T.D. wrote and edited the original draft; all co-authors reviewed and edited the manuscript. The authors have no competing interests to declare. Publisher Copyright: © 2021 The Author(s)

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

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