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, Maini, Mala K., Ogg, Graham, Knight, Julian C., Peng, Yanchun, Rowland-Jones, Sarah L. and Dong, Tao and COVID-19 Genomics UK (COG-UK) Consortium, ISARIC4C Investigators (2021) The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24 (11). ISSN 2589-0042

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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.

Item Type: Article
Additional Information: 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. 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. T.I.d.S. and T.D. conceptualized the project; T.D. T.I.d.S. L.T. and Y.P. designed and supervised T cell experiments; B.B.L. N.S.H. and M.D.P. conducted the viral sequence analyses; D.S. conducted the literature review and collated T cell epitope information; G.L. D.D. and S.C.M. performed experiments and analyzed the data; X.Y. Z.Y. A.A. and R.B. provided critical reagents and technical assistance; J.C.K. and A.J.M. established clinical cohorts; T.I.d.S. and T.D. wrote and edited the original draft; all co-authors reviewed and edited the manuscript. The authors have no competing interests to declare. Publisher Copyright: © 2021 The Author(s)
Uncontrolled Keywords: immune response,immunology,molecular biology,phylogenetics,virology,general ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School

Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > School of Health Sciences
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Depositing User: LivePure Connector
Date Deposited: 21 Sep 2022 11:30
Last Modified: 03 Nov 2022 16:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/88550
DOI: 10.1016/j.isci.2021.103353

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