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

COVID-19 Genomics UK (COG-UK) Consortium, ISARIC4C Investigators, 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, Dinesh Aggarwal, Shazaad S.Y. AhmadDavid Bibby, Vicki Chalker, Meera Chand, Gavin Dabrera, Nicholas Ellaby, Eileen Gallagher, Ian Harrison, Miren Iturriza-Gomara, Stephen P. Kidd, Angie Lackenby, Nicholas J. Loman, Nicholas W. Machin, Caoimhe McKerr, Richard Myers, Surendra Parmar, Sharon J. Peacock, Katherine A. Twohig, Anthony P. Underwood, Jake Dunning, Richard S. Tedder, Maria Zambon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number103353
JournaliScience
Volume24
Issue number11
Early online date28 Oct 2021
DOIs
Publication statusPublished - 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.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Publisher Copyright: © 2021 The Author(s).

Citation: Thushan I. de Silva et al The impact of viral mutations on recognition by SARS-CoV-2 specific T cells, iScience, Volume 24, Issue 11, 2021, 103353, ISSN 2589-0042,

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

Keywords

  • Immune response
  • Immunology
  • Molecular biology
  • Phylogenetics
  • Virology

Fingerprint

Dive into the research topics of 'The impact of viral mutations on recognition by SARS-CoV-2 specific T cells'. Together they form a unique fingerprint.

Cite this