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Nov 19, 2021;24 (11): 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 Knight, ISARIC4C Investigators, Yanchun Peng, Sarah L Rowland-Jones, Tao Dong
Author Information
  1. Thushan I de Silva: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  2. Guihai Liu: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  3. Benjamin B Lindsey: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  4. Danning Dong: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  5. Shona C Moore: NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool CH64 7TE, UK.
  6. Nienyun Sharon Hsu: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  7. Dhruv Shah: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  8. Dannielle Wellington: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  9. Alexander J Mentzer: Nuffield Department of Medicine, University of Oxford, NDM Research Building, Oxford OX3 7FZ, UK.
  10. Adrienn Angyal: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  11. Rebecca Brown: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  12. Matthew D Parker: Sheffield Bioinformatics Core, The University of Sheffield, Sheffield, UK.
  13. Zixi Ying: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  14. Xuan Yao: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  15. Lance Turtle: NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool CH64 7TE, UK.
  16. Susanna Dunachie: Centre For Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LG, UK.
  17. Mala K Maini: Division of Infection and Immunity, University College London, London WC1E 6BT, UK.
  18. Graham Ogg: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  19. Julian C Knight: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  20. Yanchun Peng: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
  21. Sarah L Rowland-Jones: The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
  22. Tao Dong: Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
PMID: 34729465 DOI: 10.1016/j.isci.2021.103353

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; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK. 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

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Grants

  1. MR/V028448/1/Medical Research Council
  2. MC_PC_19012/Medical Research Council
  3. MC_UU_00008/11/Medical Research Council
  4. MC_PC_19059/Medical Research Council
  5. 204969/Z/16/Z/Wellcome Trust
  6. MR/P011705/2/Medical Research Council
  7. 204911/Z/16/Z/Wellcome Trust
  8. MR/S032304/1/Medical Research Council
  9. /Wellcome Trust
  10. MR/R015600/1/Medical Research Council
  11. 26603/Cancer Research UK
  12. MC_UP_A090_1006/Medical Research Council
  13. MC_PC_19027/Medical Research Council
  14. MR/V001329/1/Medical Research Council
  15. MR/L018942/1/Medical Research Council
  16. G0600520/Medical Research Council
  17. G1001046/Medical Research Council
  18. MC_PC_19025/Medical Research Council
  19. MR/P011705/1/Medical Research Council
Journal Article
Article has an altmetric score of 111

Word Cloud

Created with Highcharts 10.0.0T cellCD8+variantsepitopesnucleocapsiddueepitopewithinSARS-CoV-2dataORF3alossrecognitionT cellsidentifyaminoaciddominantinterrogatingglobalsequenceSeveralarisenindependentlymultiplelineagesresultepitope-specificassessedIFN-γcytotoxickillingassaysCompleteresponsivenessseenQ213KA∗01:01-restrictedFTSDYYQLYP13LP13SP13TB∗27:05-restrictedQRNAPRITFT362IP365SA∗03:01/A∗11:01-restrictedKTFPPTEPKlinesunablerecognizevariantdiversereceptorrepertoiresdemonstratepotentialevasionhighlightneedongoingsurveillancecapableescapingwellhumoralimmunityimpactviralmutationsspecificImmuneresponseImmunologyMolecularbiologyPhylogeneticsVirology

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