TY - JOUR
T1 - The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
AU - de Silva, Thushan I.
AU - Liu, Guihai
AU - Lindsey, Benjamin B.
AU - Dong, Danning
AU - Moore, Shona C.
AU - Hsu, Nienyun Sharon
AU - Shah, Dhruv
AU - Wellington, Dannielle
AU - Mentzer, Alexander J.
AU - Angyal, Adrienn
AU - Brown, Rebecca
AU - Parker, Matthew D.
AU - Ying, Zixi
AU - Yao, Xuan
AU - Turtle, Lance
AU - Dunachie, Susanna
AU - Aanensen, David M.
AU - Abudahab, Khalil
AU - Adams, Helen
AU - Adams, Alexander
AU - Afifi, Safiah
AU - Aggarwal, Dinesh
AU - Ahmad, Shazaad S.Y.
AU - Aydin, Alp
AU - Baker, David J.
AU - Charalampous, Themoula
AU - Coupland, Lindsay
AU - Davidson, Rose K.
AU - Dervisevic, Samir
AU - Foster-Nyarko, Ebenezer
AU - Jeanes, Christopher
AU - Jones, Christopher R.
AU - Lee, David
AU - Mather, Alison E.
AU - Moore, Catherine
AU - O'Grady, Justin
AU - Page, Andrew J.
AU - Prosolek, Sophie J.
AU - Rudder, Steven
AU - Smith, Kim S.
AU - Spurgin, Lewis G.
AU - Stanley, Rachael
AU - Cole, Sarah
AU - Jones, Christopher R.
AU - Massey, Hannah
AU - Ail, Dhiraj
AU - Koduri, Gouri
AU - Price, David
AU - Shah, Aarti
AU - Smith, Richard
AU - COVID-19 Genomics UK (COG-UK) Consortium
AU - Maini, Mala K.
AU - Ogg, Graham
AU - Knight, Julian C.
AU - ISARIC4C Investigators
AU - Peng, Yanchun
AU - Rowland-Jones, Sarah L.
AU - Dong, Tao
N1 - 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.
PY - 2021/11/19
Y1 - 2021/11/19
N2 - 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.
AB - 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.
KW - Immune response
KW - Immunology
KW - Molecular biology
KW - Phylogenetics
KW - Virology
UR - https://www.scopus.com/pages/publications/85118773166
U2 - 10.1016/j.isci.2021.103353
DO - 10.1016/j.isci.2021.103353
M3 - Article
AN - SCOPUS:85118773166
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 11
M1 - 103353
ER -