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

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; COVID-19 Genomics UK (COG-UK) Consortium; Mala K Maini; Graham Ogg; Julian C Knight; ISARIC4C Investigators; Yanchun Peng; Sarah L Rowland-Jones; Tao Dong

doi:10.1016/j.isci.2021.103353

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

iScience. 2021 Nov 19;24(11):103353. doi: 10.1016/j.isci.2021.103353. Epub 2021 Oct 28.

Authors

Thushan I de Silva^{1

2}, Guihai Liu^{3

4

5}, Benjamin B Lindsey¹, Danning Dong^{3

4

6}, Shona C Moore⁷, Nienyun Sharon Hsu^{1

8}, Dhruv Shah¹, Dannielle Wellington^{3

4}, Alexander J Mentzer^{9

10}, Adrienn Angyal¹, Rebecca Brown¹, Matthew D Parker^{8

11}, Zixi Ying^{3

4}, Xuan Yao^{3

4}, Lance Turtle^{7

12}, Susanna Dunachie^{13

14}; COVID-19 Genomics UK (COG-UK) Consortium; Mala K Maini¹⁵, Graham Ogg^{3

4}, Julian C Knight^{3

9

10}; ISARIC4C Investigators; Yanchun Peng^{3

4}, Sarah L Rowland-Jones^{1

9}, Tao Dong^{3

4

9}

Collaborators

David M Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad Sy Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W Attwood, Cressida Auckland, Alp Aydin, David J Baker, Paul Baker, Carlos E Balcazar, Jonathan Ball, Jeffrey C Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H Beckett, Shaun M Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F Bronner, Ellena Brooks, Alice Broos, Julianne R Brown, Giselda Bucca, Sarah L Buchan, David Buck, Matthew Bull, Phillipa J Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M Carabelli, James S Cargill, Matthew Carlile, Silvia F Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J Chaloner, Meera Chand, Joseph G Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M Churcher, Gemma Clark, Phillip Clarke, Benjamin J Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R Connor, Kate F Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C Darby, Rose K Davidson, Alisha Davies, Robert M Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M Evans, Cariad Evans, William Everson, Derek J Fairley, Karlie Fallon, Arezou Fanaie, Ben W Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P George, Laura Gifford, Lauren Gilbert, Sophia T Girgis, Sharon Glaysher, Emily J Goldstein, Tanya Golubchik, Andrea N Gomes, Sónia Gonçalves, Ian G Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R Grant, Luke R Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N Gunson, Ravi K Gupta, Bernardo Gutierrez, Sam T Haldenby, William L Hamilton, Samantha E Hansford, Tanzina Haque, Kathryn A Harris, Ian Harrison, Ewan M Harrison, Jennifer Hart, John A Hartley, William T Harvey, Matthew Harvey, Mohammed O Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H Henderson, Andrew R Hesketh, Jessica Hey, David Heyburn, Ellen E Higginson, Verity Hill, Jack D Hill, Rachel A Hilson, Ember Hilvers, Matthew Tg Holden, Amy Hollis, Christopher W Holmes, Nadine Holmes, Alison H Holmes, Richard Hopes, Hailey R Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M Jackson, Kathryn A Jackson, David K Jackson, Aminu S Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L Kay, Sally Kay, Jon-Paul Keatley, Alexander J Keeley, Anita Kenyon, Leanne M Kermack, Manjinder Khakh, Stephen P Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A Knight, Cherian Koshy, Moritz Ug Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G Laing, Temi Lampejo, Cordelia F Langford, Deborah Lavin, Andrew I Lawton, Jack Lee, David Lee, Stefanie V Lensing, Steven Leonard, Lisa J Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J Lillie, Michelle M Lister, Rich Livett, Stephanie Lo, Nicholas J Loman, Matthew W Loose, Stavroula F Louka, Katie F Loveson, Sarah Lowdon, Hannah Lowe, Helen L Lowe, Anita O Lucaci, Catherine Ludden, Jessica Lynch, Ronan A Lyons, Katrina Lythgoe, Nicholas W Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana Ik Mahanama, Tabitha W Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T Martinez Nunez, Alison E Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M McCann, Shane A McCarthy, Kathryn McCluggage, Patrick C McClure, J T McCrone, Martin P McHugh, James P McKenna, Caoimhe McKerr, Georgina M McManus, Claire L McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L Michell, Michelle L Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J Moll, Zoltan Molnar, Irene M Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J Murray, Darren R Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O'Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J Orton, Husam Osman, Xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J Page, Emily J Park, Naomi R Park, Surendra Parmar, David G Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan Ai Payne, Sharon J Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R Price, Jacqui A Prieto, David T Pritchard, Sophie J Prosolek, Georgia Pugh, Monika Pusok, Oliver G Pybus, Hannah M Pymont, Michael A Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A Ramadan, Andrew Rambaut, John Ramble, Paul A Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L Robertson, Esther Robinson, Samuel C Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G Shepherd, Liz A Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J Sloan, Graciela Sluga, Ken Smith, Kim S Smith, Perminder Smith, Darren L Smith, Louise Smith, Colin P Smith, Nikki Smith, Katherine L Smollett, Luke B Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H Spencer Chapman, Lewis G Spurgin, Moira J Spyer, Rachael Stanley, William Stanley, Thomas D Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W Tang, Miao Tang, Ben Ew Taylor, Joshua F Taylor, Sarah Taylor, Ben Temperton, Kate E Templeton, Claire Thomas, Laura Thomson, Emma C Thomson, Alicia Thornton, Scott Aj Thurston, John A Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M Estee Torok, Jaime M Tovar-Corona, Amy Trebes, Alexander J Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A Twohig, Helen Umpleby, Anthony P Underwood, Edith E Vamos, Tetyana I Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B Vipond, Erik M Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K Watson, Sheila Waugh, Hermione J Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A Williams, Rachel J Williams, Thomas Williams, Catryn Williams, Kathleen A Williamson, Eleri Wilson-Davies, Eric Witele, Karen T Withell, Adam A Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A Yeats, Gonzalo Yebra, Wen C Yew, Gregory R Young, Jamie Young, Alex E Zarebski, Peijun Zhang, J Kenneth Baillie, Malcolm G Semple, Peter Jm Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S Cooke, Ana da Silva Filipe, Annemarie B Docherty, Gonçalo Dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A Green, William Greenhalf, Julian L Griffin, Rishi K Gupta, Ewen M Harrison, Julian A Hiscox, Antonia Ying Wai Ho, Peter W Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L 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Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis Ws Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Shona C Moore, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive 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Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young

Affiliations

¹ The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
² Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Banjul, The Gambia.
³ Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), University of Oxford, Oxford OX3 7FZ, UK.
⁴ MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
⁵ Beijing You'an Hospital, Capital Medical University, Beijing, China.
⁶ CAMS Key Laboratory of Tumor Immunology and Radiation Therapy, Xinjiang Tumor Hospital, Xinjiang Medical University, China.
⁷ NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool CH64 7TE, UK.
⁸ Sheffield Bioinformatics Core, The University of Sheffield, Sheffield, UK.
⁹ Nuffield Department of Medicine, University of Oxford, NDM Research Building, Oxford OX3 7FZ, UK.
¹⁰ Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
¹¹ Sheffield Biomedical Research Centre, The University of Sheffield, Sheffield S10 2JF, UK.
¹² Tropical & Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust (Member of Liverpool Health Partners), Liverpool L7 8XP, UK.
¹³ Centre For Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LG, UK.
¹⁴ Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
¹⁵ Division of Infection and Immunity, University College London, London WC1E 6BT, UK.

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 FTSDYYQLY_207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF_9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK_361-369. 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.

Abstract

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