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

10.1016/j.isci.2021.103353

iScience

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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.

Author list:

Affiliations

  1. 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. Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Banjul, The Gambia

  3. Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK

  4. MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK

  5. Beijing You'an Hospital, Capital Medical University, Beijing, China

  6. CAMS Key Laboratory of Tumor Immunology and Radiation Therapy, Xinjiang Tumor Hospital, Xinjiang Medical University, China

  7. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool CH64 7TE, UK

  8. Sheffield Bioinformatics Core, The University of Sheffield, Sheffield, UK

  9. Nuffield Department of Medicine, University of Oxford, NDM Research Building, Oxford OX3 7FZ, UK

  10. Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK

  11. Sheffield Biomedical Research Centre, The University of Sheffield, Sheffield S10 2JF, UK

  12. Tropical & Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust (Member of Liverpool Health Partners), Liverpool L7 8XP, UK

  13. Centre For Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LG, UK

  14. Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand

  15. https://www.cogconsortium.uk

  16. Division of Infection and Immunity, University College London, London WC1E 6BT, UK

  17. https://isaric4c.net

 

Authors

Thushan I.de Silva1,2,18,19, Guihai Liu3,4,5,18, Benjamin B.Lindsey1,18, Danning Dong3,4,6,18, Shona C.Moore7, Nienyun Sharon Hsu1,8, Dhruv Shah1, Dannielle Wellington3,4, Alexander J.Mentzer9,10, Adrienn Angyal1, Rebecca Brown1, Matthew D.Parker8,11, Zixi Ying3,4, Xuan Yao3,4, Lance Turtle7,12, Susanna Dunachie13,14, COVID-19 Genomics UK (COG-UK) Consortium15, Mala K.Maini16, Graham Ogg3,4, Julian C. Knight3,9,10, ISARIC4C Investigators17, Yanchun Peng3,4, Sarah L. Rowland-Jones1,9, Tao Dong3,4,9

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