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

de Silva, Thushan I; Liu, Guihai; Lindsey, Benjamin B; Dong, Danning; Moore, Shona C; Hsu, Nienyun Sharon; Shah, Dhruv; Wellington, Dannielle; Mentzer, Alexander J; Angyal, Adrienn; Brown, Rebecca; Parker, Matthew D; Ying, Zixi; Yao, Xuan; Turtle, Lance; Dunachie, Susanna; COVID-19 Genomics UK (COG-UK) Consortium; Maini, Mala K; Ogg, Graham; Knight, Julian C; ISARIC4C Investigators; Peng, Yanchun; Rowland-Jones, Sarah L; Dong, Tao

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Authors

de Silva, Thushan I

Liu, Guihai

Lindsey, Benjamin B

Dong, Danning

Moore, Shona C

Hsu, Nienyun Sharon

Shah, Dhruv

Publication Date

2021-11-19

Journal Title

iScience

ISSN

2589-0042

Publisher

Elsevier BV

Volume

Issue

Pages

103353

Language

eng

Type

Article

This Version

VoR

Metadata

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Citation

de Silva, T. I., Liu, G., Lindsey, B. B., Dong, D., Moore, S. C., Hsu, N. S., Shah, D., et al. (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

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

Sponsorship

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 Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (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 Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (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 ResearchCentre (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 Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC.

Funder references

MRC (MC_PC_19027)

Medical Research Council (MC_PC_19027)

Medical Research Council (MR/P011705/1)

MRC (via University of Birmingham) (MR/V028448/1)

Identifiers

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

This record's URL: https://www.repository.cam.ac.uk/handle/1810/330571

Rights

Attribution 4.0 International

Licence URL: https://creativecommons.org/licenses/by/4.0/

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