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

de Silva, Thushan, 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, Bashton, Matthew, McCann, Clare, Nelson, Andrew, Smith, Darren, Yew, Wen Chyin, Young, Greg, The COVID-19 Genomics UK (COG-UK) Consortium, and ISARIC4C Investigators, (2021) The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24 (11). p. 103353. ISSN 2589-0042

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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.

Item Type: Article
Additional Information: Matthew Bashton, Andrew Nelson, Clare McCann, Greg Young and Darren Smith are members of the COVID-19 Genomics UK consortium. 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 MCPC19059). J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS.
Uncontrolled Keywords: Immune response, Virology, Molecular biology, Phylogenetics
Subjects: A300 Clinical Medicine
A900 Others in Medicine and Dentistry
C100 Biology
C900 Others in Biological Sciences
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Rachel Branson
Date Deposited: 19 Nov 2021 14:21
Last Modified: 19 Nov 2021 14:30

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