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

Marc-Emmanuel Dumas (1, 1, 2) , Thushan de Silva , Guihai Liu , Benjamin Lindsey , Danning Dong , Shona Moore , Nienyun Sharon Hsu , Dhruv Shah , Dannielle Wellington , Alexander Mentzer , Adrienn Angyal , Rebecca Brown , Matthew Parker , Zixi Ying , Xuan Yao , Lance Turtle , Susanna Dunachie , Mala Maini , Graham Ogg , Julian Knight , Yanchun Peng , Sarah Rowland-Jones , Tao Dong , David Aanensen , Khalil Abudahab , Helen Adams , Alexander Adams , Safiah Afifi , Dinesh Aggarwal , Shazaad S.Y. Ahmad , Louise Aigrain , Adela Alcolea-Medina , Nabil-Fareed Alikhan , Elias Allara , Roberto Amato , Tara Annett , Stephen Aplin , Cristina Ariani , Hibo Asad , Amy Ash , Paula Ashfield , Fiona Ashford , Laura Atkinson , Stephen Attwood , Cressida Auckland , Alp Aydin , David Baker , Paul Baker , Carlos Balcazar , Jonathan Ball , Jeffrey Barrett , Magdalena Barrow , Edward Barton , Matthew Bashton , Andrew Bassett , Rahul Batra , Chris Baxter , Nadua Bayzid , Charlotte Beaver , Angela Beckett , Shaun Beckwith , Luke Bedford , Robert Beer , Andrew Beggs , Katherine Bellis , Louise Berry , Beatrice Bertolusso , Angus Best , Emma Betteridge , David Bibby , Kelly Bicknell , Debbie Binns , Alec Birchley , Paul 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 Bradley , Cassie Breen , Catherine Bresner , Judith Breuer , Stephen Bridgett , Iraad Bronner , Ellena Brooks , Alice Broos , Julianne Brown , Giselda Bucca , Sarah Buchan , David Buck , Matthew Bull , Phillipa Burns , Shirelle Burton-Fanning , Timothy Byaruhanga , Matthew Byott , Sharon Campbell , Alessandro Carabelli , James Cargill , Matthew Carlile , Silvia Carvalho , Anna Casey , Anibolina Castigador , Jana Catalan , Vicki Chalker , Nicola Chaloner , Meera Chand , Joseph Chappell , Themoula Charalampous , Wendy Chatterton , Yasmin Chaudhry , Carol Churcher , Gemma Clark , Phillip Clarke , Benjamin Cogger , Kevin Cole , Jennifer Collins , Rachel Colquhoun , Thomas Connor , Kate 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 Crown , Dorian Crudgington , Nicola Cumley , Tanya Curran , Martin Curran , Ana da Silva Filipe , Gavin Dabrera , Alistair Darby , Rose Davidson , Alisha Davies , Robert 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 Dorman , Fatima Downing , Megan Driscoll , Louis Du Plessis , Nichola Duckworth , Jillian Durham , Kirstine Eastick , Lisa Easton , Richard Eccles , Jonathan Edgeworth , Sue Edwards , Kate El Bouzidi , Sahar Eldirdiri , Nicholas Ellaby , Scott Elliott , Gary Eltringham , Leah Ensell , Michelle Erkiert , Marina Escalera Zamudio , Sarah Essex , Johnathan Evans , Cariad Evans , William Everson , Derek Fairley , Karlie Fallon , Arezou Fanaie , Ben Farr , Christopher Fearn , Theresa Feltwell , Lynne Ferguson , Laia Fina , Flavia Flaviani , Vicki Fleming , Sally Forrest , Ebenezer Foster-Nyarko , Benjamin Foulkes , Luke Foulser , Mireille Fragakis , Dan Frampton , Sarah Francois , Christophe Fraser , Timothy Freeman , Helen Fryer , Marc Fuchs , William Fuller , Kavitha Gajee , Katerina Galai , Abbie Gallagher , Eileen Gallagher , Michael Gallagher , Marta Gallis , Amy Gaskin , Bree Gatica-Wilcox , Lily Geidelberg , Matthew Gemmell , Iliana Georgana , Ryan George , Laura Gifford , Lauren Gilbert , Sophia Girgis , Sharon Glaysher , Emily Goldstein , Tanya Golubchik , Andrea Gomes , Sónia Gonçalves , Ian Goodfellow , Scott Goodwin , Salman Goudarzi , Marina Gourtovaia , Clive Graham , Lee Graham , Paul Grant , Luke Green , Angie Green , Jane Greenaway , Richard Gregory , Martyn Guest , Rory Gunson , Ravi Gupta , Bernardo Gutierrez , Sam Haldenby , William Hamilton , Samantha Hansford , Tanzina Haque , Kathryn Harris , Ian Harrison , Ewan Harrison , Jennifer Hart , John Hartley , William Harvey , Matthew Harvey , Mohammed Hassan-Ibrahim , Judith Heaney , Thomas Helmer , John Henderson , Andrew Hesketh , Jessica Hey , David Heyburn , Ellen Higginson , Verity Hill , Jack Hill , Rachel Hilson , Ember Hilvers , Matthew T.G. Holden , Amy Hollis , Christopher Holmes , Nadine Holmes , Alison Holmes , Richard Hopes , Hailey Hornsby , Myra Hosmillo , Catherine Houlihan , Hannah Howson-Wells , Jonathan Hubb , Hannah Huckson , Warwick Hughes , Joseph Hughes , Margaret Hughes , Stephanie Hutchings , Giles Idle , Chris Illingworth , Robert Impey , Dianne Irish-Tavares , Miren Iturriza-Gomara , Rhys Izuagbe , Chris Jackson , Ben Jackson , Leigh Jackson , Kathryn Jackson , David Jackson , Aminu Jahun , Victoria James , Keith James , Christopher Jeanes , Aaron Jeffries , Sarah Jeremiah , Andrew Jermy , Michaela John , Rob Johnson , Kate Johnson , Ian Johnston , Owen Jones , Sophie Jones , Hannah Jones , Christopher Jones , Neil Jones , Amelia Joseph , Sarah Judges , Gemma Kay , Sally Kay , Jon-Paul Keatley , Alexander Keeley , Anita Kenyon , Leanne Kermack , Manjinder Khakh , Stephen Kidd , Maimuna Kimuli , Stuart Kirk , Christine Kitchen , Katie Kitchman , Bridget Knight , Cherian Koshy , Moritz U.G. Kraemer , Sara Kumziene-Summerhayes , Dominic Kwiatkowski , Angie Lackenby , Kenneth Laing , Temi Lampejo , Cordelia Langford , Deborah Lavin , Andrew Lawton , Jack Lee , David Lee , Stefanie Lensing , Steven Leonard , Lisa Levett , Thanh Le-Viet , Jonathan Lewis , Kevin Lewis , Jennifier Liddle , Steven Liggett , Patrick Lillie , Michelle Lister , Rich Livett , Stephanie Lo , Nicholas Loman , Matthew Loose , Stavroula Louka , Katie Loveson , Sarah Lowdon , Hannah Lowe , Helen Lowe , Anita Lucaci , Catherine Ludden , Jessica Lynch , Ronan Lyons , Katrina Lythgoe , Nicholas Machin , George Macintyre-Cockett , Andrew Mack , Ben Macklin , Alasdair Maclean , Emily Macnaughton , Pinglawathee Madona , Mailis Maes , Laurentiu Maftei , Adhyana I.K. Mahanama , Tabitha Mahungu , Daniel Mair , Joshua Maksimovic , Cassandra Malone , Daniel Maloney , Nikos Manesis , Robin Manley , Anna Mantzouratou , Angela Marchbank , Arun Mariappan , Inigo Martincorena , Rocio Martinez Nunez , Alison Mather , Patrick Maxwell , Megan Mayhew , Tamyo Mbisa , Clare Mccann , Shane Mccarthy , Kathryn Mccluggage , Patrick Mcclure , J.T. Mccrone , Martin Mchugh , James Mckenna , Caoimhe Mckerr , Georgina Mcmanus , Claire Mcmurray , Alan Mcnally , Lizzie Meadows , Nathan Medd , Oliver Megram , Mirko Menegazzo , Ian Merrick , Stephen Michell , Michelle Michelsen , Mariyam Mirfenderesky , Jeremy Mirza , Julia Miskelly , Emma Moles-Garcia , Robin Moll , Zoltan Molnar , Irene 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 Murray , Darren 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 Orton , Husam Osman , Nicole Pacchiarini , Debra Padgett , Andrew Page , Emily Park , Naomi Park , Surendra Parmar , David Partridge , David Pascall , Amita Patel , Bindi Patel , Steve Paterson , Brendan A.I. Payne , Sharon Peacock , Clare Pearson , Emanuela Pelosi , Benita Percival , Jon Perkins , Malorie Perry , Malte Pinckert , Steven Platt , Olga Podplomyk , Manoj Pohare , Marcus Pond , Cassie Pope , Radoslaw Poplawski , Jessica Powell , Jennifer Poyner , Liam Prestwood , Anna Price , James Price , Jacqui Prieto , David Pritchard , Sophie Prosolek , Georgia Pugh , Monika Pusok , Oliver Pybus , Hannah Pymont , Michael Quail , Joshua Quick , Clara Radulescu , Jayna Raghwani , Manon Ragonnet-Cronin , Lucille Rainbow , Diana Rajan , Shavanthi Rajatileka , Newara Ramadan , Andrew Rambaut , John Ramble , Paul Randell , Liz Ratcliffe , Veena Raviprakash , Mohammad Raza , Nicholas Redshaw , Sara Rey , Nicola Reynolds , Alex Richter , David Robertson , Esther Robinson , Samuel Robson , Fiona Rogan , Stefan Rooke , Will Rowe , Sunando Roy , Steven Rudder , Chris Ruis , Steven Rushton , Felicity Ryan , Kordo Saeed , Buddhini Samaraweera , Christine 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 Shepherd , Liz Sheridan , Nicola Sheriff , Lesley Shirley , John Sillitoe , Siona Silviera , David Simpson , Aditi Singh , Dawn Singleton , Timofey Skvortsov , Tim Sloan , Graciela Sluga , Ken Smith , Kim Smith , Perminder Smith , Darren Smith , Louise Smith , Colin Smith , Nikki Smith , Katherine Smollett , Luke Snell , Thomas Somassa , Joel Southgate , Karla Spellman , Michael Spencer Chapman , Lewis Spurgin , Moira Spyer , Rachael Stanley , William Stanley , Thomas Stanton , Igor Starinskij , Joanne Stockton , Susanne Stonehouse , Nathaniel Storey , David Studholme , Malur Sudhanva , Emma Swindells , Yusri Taha , Ngee Keong Tan , Julian Tang , Miao Tang , Ben E.W. Taylor , Joshua Taylor , Sarah Taylor , Ben Temperton , Kate Templeton , Claire Thomas , Laura Thomson , Emma Thomson , Alicia Thornton , Scott A.J. Thurston , John Todd , Rachael Tomb , Lily Tong , Gerry Tonkin-Hill , M. Estee Torok , Jaime Tovar-Corona , Amy Trebes , Alexander Trotter , Ioulia Tsatsani , Robyn Turnbull , Katherine Twohig , Helen Umpleby , Anthony Underwood , Edith Vamos , Tetyana Vasylyeva , Sreenu Vattipally , Gabrielle Vernet , Barry Vipond , Erik Volz , Sarah Walsh , Dennis Wang , Ben Warne , Joanna Warwick-Dugdale , Elizabeth Wastnedge , Joanne Watkins , Louisa Watson , Sheila Waugh , Hermione Webster , Danni Weldon , Elaine Westwick , Thomas Whalley , Helen Wheeler , Mark Whitehead , Max Whiteley , Andrew Whitwham , Claudia Wierzbicki , Nicholas Willford , Lesley-Anne Williams , Rebecca Williams , Cheryl Williams , Chris Williams , Charlotte Williams , Rachel Williams , Thomas Williams , Catryn Williams , Kathleen Williamson , Eleri Wilson-Davies , Eric Witele , Karen Withell , Adam Witney , Paige Wolverson , Nick Wong , Trudy Workman , Victoria Wright , Derek Wright , Tim Wyatt , Sarah Wyllie , Li Xu-Mccrae , Mehmet Yavus , Geraldine Yaze , Corin Yeats , Gonzalo Yebra , Wen Yew , Gregory Young , Jamie Young , Alex Zarebski , Peijun Zhang , J. Kenneth Baillie , Malcolm Semple , Peter J.M. Openshaw , Gail Carson , Beatrice Alex , Petros Andrikopoulos , Benjamin Bach , Wendy Barclay , Debby Bogaert , Kanta Chechi , Graham Cooke , Annemarie Docherty , Gonçalo dos Santos Correia , Jake Dunning , Tom Fletcher , Christopher Green , William Greenhalf , Julian Griffin , Rishi Gupta , Ewen Harrison , Julian Hiscox , Antonia Ying Wai Ho , Peter Horby , Samreen Ijaz , Saye Khoo , Paul Klenerman , Andrew Law , Matthew Lewis , Sonia Liggi , Wei Shen Lim , Lynn Maslen , Laura Merson , Alison Meynert , Mahdad Noursadeghi , Michael Olanipekun , Anthonia Osagie , Massimo Palmarini , Carlo Palmieri , William Paxton , Georgios Pollakis , Nicholas Price , Clark Russell , Vanessa Sancho-Shimizu , Caroline Sands , Janet Scott , Louise Sigfrid , Tom Solomon , Shiranee Sriskandan , David Stuart , Charlotte Summers , Olivia Swann , Zoltan Takats , Panteleimon Takis , Richard Tedder , A.A. Roger Thompson , Ryan Thwaites , Maria Zambon , Hayley Hardwick , Chloe Donohue , Fiona Griffiths , Wilna Oosthuyzen , Cara Donegan , Rebecca Spencer , Jo Dalton , Michelle Girvan , Egle Saviciute , Stephanie Roberts , Janet Harrison , Laura Marsh , Marie Connor , Sophie Halpin , Clare Jackson , Carrol Gamble , Daniel Plotkin , James Lee , Gary Leeming , Murray Wham , Sara Clohisey , Ross Hendry , James Scott-Brown , Victoria Shaw , Sarah Mcdonald , Seán Keating , Katie Ahmed , Jane Armstrong , Milton Ashworth , Innocent Asiimwe , Siddharth Bakshi , Samantha Barlow , Laura Booth , Benjamin Brennan , Katie Bullock , Benjamin W.A. Catterall , Jordan Clark , Emily Clarke , Sarah Cole , Louise Cooper , Helen Cox , Christopher Davis , Oslem Dincarslan , Chris Dunn , Philip Dyer , Angela Elliott , Anthony Evans , Lorna Finch , Lewis W.S. Fisher , Terry Foster , Isabel Garcia-Dorival , Philip Gunning , Catherine Hartley , Rebecca Jensen , Trevor Jones , Shadia Khandaker , Katharine King , Robyn Kiy , Chrysa Koukorava , Annette Lake , Suzannah Lant , Diane Latawiec , Lara Lavelle-Langham , Daniella Lefteri , Lauren Lett , Lucia Livoti , Maria Mancini , Laurence Mcevoy , John Mclauchlan , Soeren Metelmann , Nahida Miah , Joanna Middleton , Joyce Mitchell , Ellen Murphy , Rebekah Penrice-Randal , Jack Pilgrim , Tessa Prince , Will Reynolds , P. Matthew Ridley , Debby Sales , Rebecca Shears , Benjamin Small , Krishanthi 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 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 , Duncan Chambler , Nigel Chee , Jenny Child , Srikanth Chukkambotla , Tom Clark , Paul Collini , Catherine Cosgrove , Jason Cupitt , Maria-Teresa Cutino-Moguel , Paul Dark , Chris Dawson , Phil Donnison , Sam Douthwaite , Andrew Drummond , Ingrid Durand , Ahilanadan Dushianthan , Tristan Dyer , Chi Eziefula , Chrisopher Fegan , Adam Finn , Duncan Fullerton , Sanjeev Garg , Atul Garg , Effrossyni Gkrania-Klotsas , Jo Godden , Arthur Goldsmith , Elaine Hardy , Stuart Hartshorn , Daniel Harvey , Peter Havalda , Daniel Hawcutt , Maria Hobrok , Luke Hodgson , Anil Hormis , Michael Jacobs , Susan Jain , Paul Jennings , Agilan Kaliappan , Vidya Kasipandian , Stephen Kegg , Michael Kelsey , Jason Kendall , Caroline Kerrison , Ian Kerslake , Oliver Koch , Gouri Koduri , George Koshy , Shondipon Laha , Steven Laird , Susan Larkin , Tamas Leiner , James Limb , Vanessa Linnett , Jeff Little , Mark Lyttle , Michael Macmahon , Ravish Mankregod , Huw Masson , Elijah Matovu , Katherine Mccullough , Ruth Mcewen , Manjula Meda , Gary Mills , Jane Minton , Kavya Mohandas , Quen Mok , James Moon , Elinoor Moore , Patrick Morgan , Craig Morris , Katherine Mortimore , Mbiye Mpenge , Rohinton Mulla , Michael Murphy , Megan Nagel , Thapas Nagarajan , Mark Nelson , Lillian Norris , Matthew O'Shea , Igor Otahal , Marlies Ostermann , Mark Pais , Selva Panchatsharam , Danai Papakonstantinou , Hassan Paraiso , Brij Patel , Natalie Pattison , Justin Pepperell , Mark Peters , Mandeep Phull , Stefania Pintus , Jagtur Singh Pooni , Tim Planche , Frank Post , David Price , Rachel Prout , Nikolas Rae , Henrik Reschreiter , Tim Reynolds , Neil Richardson , Mark Roberts , Devender Roberts , Alistair Rose , Guy Rousseau , Bobby Ruge , Brendan Ryan , Taranprit Saluja , Matthias Schmid , Aarti Shah , Prad Shanmuga , Anil Sharma , Anna Shawcross , Jeremy Sizer , Manu Shankar-Hari , Richard Smith , Catherine Snelson , Nick Spittle , Nikki Staines , Tom Stambach , Richard Stewart , Pradeep Subudhi , Tamas Szakmany , Kate Tatham , Jo Thomas , Chris Thompson , Robert Thompson , Ascanio Tridente , Darell Tupper-Carey , Mary Twagira , Nick Vallotton , Rama Vancheeswaran , Lisa Vincent-Smith , Shico Visuvanathan , Alan Vuylsteke , Sam Waddy , Rachel Wake , Andrew Walden , Ingeborg Welters , Tony Whitehouse , Paul Whittaker , Ashley Whittington , Padmasayee Papineni , Meme Wijesinghe , Martin Williams , Lawrence Wilson , Stephen Winchester , Martin Wiselka , Adam Wolverson , Daniel Wootton , Andrew Workman , Bryan Yates , Peter Young

1 Imperial College London
2 CNRS - Centre National de la Recherche Scientifique

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.

Mots clés: Immune response; Immunology; Molecular biology; Phylogenetics; Virology

Domaines: Biochimie [q-bio.BM]; Immunologie

Marc-Emmanuel Dumas, Thushan de Silva, Guihai Liu, Benjamin Lindsey, Danning Dong, et al.. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 2021, 24 (11), pp.103353. ⟨10.1016/j.isci.2021.103353⟩. ⟨hal-03451248⟩