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

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.

Metadata

Authors/Creators:	de Silva, TI https://orcid.org/0000-0002-6498-9212 Liu, G Lindsey, BB https://orcid.org/0000-0003-4227-2592 Dong, D Moore, SC Hsu, NS Shah, D Wellington, D Mentzer, AJ Angyal, A Brown, R Parker, MD Ying, Z Yao, X Turtle, L Dunachie, S Maini, MK Ogg, G Knight, JC Peng, Y Rowland-Jones, SL Dong, T Aanensen, DM Abudahab, K Adams, H Adams, A Afifi, S Aggarwal, D Ahmad, SSY Aigrain, L Alcolea-Medina, A Alikhan, N-F Allara, E Amato, R Annett, T Aplin, S Ariani, CV Asad, H Ash, A Ashfield, P Ashford, F Atkinson, L Attwood, SW Auckland, C Aydin, A Baker, DJ Baker, P Balcazar, CE Ball, J Barrett, JC Barrow, M Barton, E Bashton, M Bassett, AR Batra, R Baxter, C Bayzid, N Beaver, C Beckett, AH Beckwith, SM Bedford, L Beer, R Beggs, A Bellis, KL Berry, L Bertolusso, B Best, A Betteridge, E Bibby, D Bicknell, K Binns, D Birchley, A Bird, PW Bishop, C Blacow, R Blakey, V Blane, B Bolt, F Bonfield, J Bonner, S Bonsall, D Boswell, T Bosworth, A Bourgeois, Y Boyd, O Bradley, DT Breen, C Bresner, C Breuer, J Bridgett, S Bronner, IF Brooks, E Broos, A Brown, JR Bucca, G Buchan, SL Buck, D Bull, M Burns, PJ Burton-Fanning, S Byaruhanga, T Byott, M Campbell, S Carabelli, AM Cargill, JS Carlile, M Carvalho, SF Casey, A Castigador, A Catalan, J Chalker, V Chaloner, NJ Chand, M Chappell, JG Charalampous, T Chatterton, W Chaudhry, Y Churcher, CM Clark, G Clarke, P Cogger, BJ Cole, K Collins, J Colquhoun, R Connor, TR Cook, KF Coombes, J Corden, S Cormie, C Cortes, N Cotic, M Cotton, S Cottrell, S Coupland, L Cox, M Cox, A Craine, N Crawford, L Cross, A Crown, MR Crudgington, D Cumley, N Curran, T Curran, MD da Silva Filipe, A Dabrera, G Darby, AC Davidson, RK Davies, A Davies, RM Davis, T de Angelis, D De Lacy, E de Oliveira Martins, L Debebe, J Denton-Smith, R Dervisevic, S Dewar, R Dey, J Dias, J Dobie, D Dorman, MJ Downing, F Driscoll, M du Plessis, L Duckworth, N Durham, J Eastick, K Easton, LJ Eccles, R Edgeworth, J Edwards, S El Bouzidi, K Eldirdiri, S Ellaby, N Elliott, S Eltringham, G Ensell, L Erkiert, MJ Zamudio, ME Essex, S Evans, JM Evans, C Everson, W Fairley, DJ Fallon, K Fanaie, A Farr, BW Fearn, C Feltwell, T Ferguson, L Fina, L Flaviani, F Fleming, VM Forrest, S Foster-Nyarko, E Foulkes, BH Foulser, L Fragakis, M Frampton, D Francois, S Fraser, C Freeman, TM Fryer, H Fuchs, M Fuller, W Gajee, K Galai, K Gallagher, A Gallagher, E Gallagher, MD Gallis, M Gaskin, A Gatica-Wilcox, B Geidelberg, L Gemmell, M Georgana, I George, RP Gifford, L Gilbert, L Girgis, ST Glaysher, S Goldstein, EJ Golubchik, T Gomes, AN Gonçalves, S Goodfellow, IG Goodwin, S Goudarzi, S Gourtovaia, M Graham, C Graham, L Grant, PR Green, LR Green, A Greenaway, J Gregory, R Guest, M Gunson, RN Gupta, RK Gutierrez, B Haldenby, ST Hamilton, WL Hansford, SE Haque, T Harris, KA Harrison, I Harrison, EM Hart, J Hartley, JA Harvey, WT Harvey, M Hassan-Ibrahim, MO Heaney, J Helmer, T Henderson, JH Hesketh, AR Hey, J Heyburn, D Higginson, EE Hill, V Hill, JD Hilson, RA Hilvers, E Holden, MTG Hollis, A Holmes, CW Holmes, N Holmes, AH Hopes, R Hornsby, HR Hosmillo, M Houlihan, C Howson-Wells, HC Hubb, J Huckson, H Hughes, W Hughes, J Hughes, M Hutchings, S Idle, G Illingworth, CJ Impey, R Irish-Tavares, D Iturriza-Gomara, M Izuagbe, R Jackson, C Jackson, B Jackson, LM Jackson, KA Jackson, DK Jahun, AS James, V James, K Jeanes, C Jeffries, AR Jeremiah, S Jermy, A John, M Johnson, R Johnson, K Johnston, I Jones, O Jones, S Jones, H Jones, CR Jones, N Joseph, A Judges, S Kay, GL Kay, S Keatley, J-P Keeley, AJ Kenyon, A Kermack, LM Khakh, M Kidd, SP Kimuli, M Kirk, S Kitchen, C Kitchman, K Knight, BA Koshy, C Kraemer, MUG Kumziene-Summerhayes, S Kwiatkowski, D Lackenby, A Laing, KG Lampejo, T Langford, CF Lavin, D Lawton, AI Lee, J Lee, D Lensing, SV Leonard, S Levett, LJ Le-Viet, T Lewis, J Lewis, K Liddle, J Liggett, S Lillie, PJ Lister, MM Livett, R Lo, S Loman, NJ Loose, MW Louka, SF Loveson, KF Lowdon, S Lowe, H Lowe, HL Lucaci, AO Ludden, C Lynch, J Lyons, RA Lythgoe, K Machin, NW MacIntyre-Cockett, G Mack, A Macklin, B Maclean, A Macnaughton, E Madona, P Maes, M Maftei, L Mahanama, AIK Mahungu, TW Mair, D Maksimovic, J Malone, CS Maloney, D Manesis, N Manley, R Mantzouratou, A Marchbank, A Mariappan, A Martincorena, I Martinez Nunez, RT Mather, AE Maxwell, P Mayhew, M Mbisa, T McCann, CM McCarthy, SA McCluggage, K McClure, PC McCrone, JT McHugh, MP McKenna, JP McKerr, C McManus, GM McMurray, CL McMurray, C McNally, A Meadows, L Medd, N Megram, O Menegazzo, M Merrick, I Michell, SL Michelsen, ML Mirfenderesky, M Mirza, J Miskelly, J Moles-Garcia, E Moll, RJ Molnar, Z Monahan, IM Mondani, M Mookerjee, S Moore, C Moore, J Moore, N Moore, C Morcrette, H Morgan, S Morgan, M Mori, M Morriss, A Moses, S Mower, C Muir, P Mukaddas, A Munemo, F Munn, R Murray, A Murray, LJ Murray, DR Mutingwende, M Myers, R Nastouli, E Nebbia, G Nelson, A Nelson, C Nicholls, S Nichols, J Nicodemi, R Nomikou, K O’Grady, J O'Brien, S Odedra, M Ohemeng-Kumi, N Oliver, K Orton, RJ Osman, H xeine O'Toole Pacchiarini, N Padgett, D Page, AJ Park, EJ Park, NR Parmar, S Partridge, DG Pascall, D Patel, A Patel, B Paterson, S Payne, BAI Peacock, SJ Pearson, C Pelosi, E Percival, B Perkins, J Perry, M Pinckert, ML Platt, S Podplomyk, O Pohare, M Pond, M Pope, CF Poplawski, R Powell, J Poyner, J Prestwood, L Price, A Price, JR Prieto, JA Pritchard, DT Prosolek, SJ Pugh, G Pusok, M Pybus, OG Pymont, HM Quail, MA Quick, J Radulescu, C Raghwani, J Ragonnet-Cronin, M Rainbow, L Rajan, D Rajatileka, S Ramadan, NA Rambaut, A Ramble, J Randell, PA Randell, P Ratcliffe, L Raviprakash, V Raza, M Redshaw, NM Rey, S Reynolds, N Richter, A Robertson, DL Robinson, E Robson, SC Rogan, F Rooke, S Rowe, W Roy, S Rudder, S Ruis, C Rushton, S Ryan, F Saeed, K Samaraweera, B Sambles, CM Sanderson, R Sanderson, T Sang, F Sass, T Scher, E Scott, G Scott, C Sehmi, J Shaaban, S Shah, D Shaw, J Shelest, E Shepherd, JG Sheridan, LA Sheriff, N Shirley, L Sillitoe, J Silviera, S Simpson, DA Singh, A Singleton, D Skvortsov, T Sloan, TJ Sluga, G Smith, K Smith, KS Smith, P Smith, DL Smith, L Smith, CP Smith, N Smollett, KL Snell, LB Somassa, T Southgate, J Spellman, K Spencer Chapman, MH Spurgin, LG Spyer, MJ Stanley, R Stanley, W Stanton, TD Starinskij, I Stockton, J Stonehouse, S Storey, N Studholme, DJ Sudhanva, M Swindells, E Taha, Y Tan, NK Tang, JW Tang, M Taylor, BEW Taylor, JF Taylor, S Temperton, B Templeton, KE Thomas, C Thomson, L Thomson, EC Thornton, A Thurston, SAJ Todd, JA Tomb, R Tong, L Tonkin-Hill, G Torok, ME Tovar-Corona, JM Trebes, A Trotter, AJ Tsatsani, I Turnbull, R Twohig, KA Umpleby, H Underwood, AP Vamos, EE Vasylyeva, TI Vattipally, S Vernet, G Vipond, BB Volz, EM Walsh, S Wang, D https://orcid.org/0000-0003-0068-1005 Warne, B Warwick-Dugdale, J Wastnedge, E Watkins, J Watson, LK Waugh, S Webster, HJ Weldon, D Westwick, E Whalley, T Wheeler, H Whitehead, M Whiteley, M Whitwham, A Wierzbicki, C Willford, NJ Williams, L-A Williams, R Williams, C Williams, C Williams, CA Williams, RJ Williams, T Williams, C Williamson, KA Wilson-Davies, E Witele, E Withell, KT Witney, AA Wolverson, P Wong, N Workman, T Wright, V Wright, DW Wyatt, T Wyllie, S Xu-McCrae, L Yavus, M Yaze, G Yeats, CA Yebra, G Yew, WC Young, GR Young, J Zarebski, AE Zhang, P Baillie, JK Semple, MG Openshaw, PJM Carson, G Alex, B Andrikopoulos, P Bach, B Barclay, WS Bogaert, D Chand, M Chechi, K Cooke, GS da Silva Filipe, A Docherty, AB Correia, GDS Dumas, M-E Dunning, J Fletcher, T Green, CA Greenhalf, W Griffin, JL Gupta, RK Harrison, EM Hiscox, JA Wai Ho, AY Horby, PW Ijaz, S Khoo, S Klenerman, P Law, A Lewis, MR Liggi, S Lim, WS Maslen, L Mentzer, AJ Merson, L Meynert, AM Noursadeghi, M Olanipekun, M Osagie, A Palmarini, M Palmieri, C Paxton, WA Pollakis, G Price, N Rambaut, A Robertson, DL Russell, CD Sancho-Shimizu, V Sands, CJ Scott, JT Sigfrid, L Solomon, T Sriskandan, S Stuart, D Summers, C Swann, OV Takats, Z Takis, P Tedder, RS Thompson, AAR Thomson, EC Thwaites, RS Zambon, M Hardwick, H Donohue, C Griffiths, F Oosthuyzen, W Donegan, C Spencer, RG Dalton, J Girvan, M Saviciute, E Roberts, S Harrison, J Marsh, L Connor, M Halpin, S Jackson, C Gamble, C Plotkin, D Lee, J Leeming, G Law, A Wham, M Clohisey, S Hendry, R Scott-Brown, J Shaw, V McDonald, SE Keating, S Ahmed, KA Armstrong, JA Ashworth, M Asiimwe, IG Bakshi, S Barlow, SL Booth, L Brennan, B Bullock, K Catterall, BWA Clark, JJ Clarke, EA Cole, S Cooper, L Cox, H Davis, C Dincarslan, O Dunn, C Dyer, P Elliott, A Evans, A Finch, L Fisher, LWS Foster, T Garcia-Dorival, I Gunning, P Hartley, C Jensen, RL Jones, CB Jones, TR Khandaker, S King, K Kiy, RT Koukorava, C Lake, A Lant, S Latawiec, D Lavelle-Langham, L Lefteri, D Lett, L Livoti, LA Mancini, M McDonald, S McEvoy, L McLauchlan, J Metelmann, S Miah, NS Middleton, J Mitchell, J Moore, SC Murphy, EG Penrice-Randal, R Pilgrim, J Prince, T Reynolds, W Ridley, PM Sales, D Shaw, VE Shears, RK Small, B Subramaniam, KS Szemiel, A Taggart, A Tanianis-Hughes, J Thomas, J Trochu, E van Tonder, L Wilcock, E Zhang, JE Flaherty, L Maziere, N Cass, E Carracedo, AD Carlucci, N Holmes, A Massey, H Murphy, L Wrobel, N McCafferty, S Morrice, K MacLean, A Adeniji, K Agranoff, D Agwuh, K Ail, D Aldera, EL Alegria, A Allen, S Angus, B Ashish, A Atkinson, D Bari, S Barlow, G Barnass, S Barrett, N Bassford, C Basude, S Baxter, D Beadsworth, M Bernatoniene, J Berridge, J Berry, C Best, N Bothma, P Chadwick, D Brittain-Long, R Bulteel, N Burden, T Burtenshaw, A Caruth, V Chadwick, D Chambler, D Chee, N Child, J Chukkambotla, S Clark, T Collini, P Cosgrove, C Cupitt, J Cutino-Moguel, M-T Dark, P Dawson, C Dervisevic, S Donnison, P Douthwaite, S Drummond, A DuRand, I Dushianthan, A Dyer, T Evans, C Eziefula, C Fegan, C Finn, A Fullerton, D Garg, S Garg, S Garg, A Gkrania-Klotsas, E Godden, J Goldsmith, A Graham, C Hardy, E Hartshorn, S Harvey, D Havalda, P Hawcutt, DB Hobrok, M Hodgson, L Hormis, A Jacobs, M Jain, S Jennings, P Kaliappan, A Kasipandian, V Kegg, S Kelsey, M Kendall, J Kerrison, C Kerslake, I Koch, O Koduri, G Koshy, G Laha, S Laird, S Larkin, S Leiner, T Lillie, P Limb, J Linnett, V Little, J Lyttle, M MacMahon, M MacNaughton, E Mankregod, R Masson, H Matovu, E McCullough, K McEwen, R Meda, M Mills, G Minton, J Mirfenderesky, M Mohandas, K Mok, Q Moon, J Moore, E Morgan, P Morris, C Mortimore, K Moses, S Mpenge, M Mulla, R Murphy, M Nagel, M Nagarajan, T Nelson, M Norris, L O'Shea, MK Otahal, I Ostermann, M Pais, M Palmieri, C Panchatsharam, S Papakonstantinou, D Paraiso, H Patel, B Pattison, N Pepperell, J Peters, M Phull, M Pintus, S Pooni, JS Planche, T Post, F Price, D Prout, R Rae, N Reschreiter, H Reynolds, T Richardson, N Roberts, M Roberts, D Rose, A Rousseau, G Ruge, B Ryan, B Saluja, T Schmid, ML Shah, A Shanmuga, P Sharma, A Shawcross, A Sizer, J Shankar-Hari, M Smith, R Snelson, C Spittle, N Staines, N Stambach, T Stewart, R Subudhi, P Szakmany, T Tatham, K Thomas, J Thompson, C Thompson, R Tridente, A Tupper-Carey, D Twagira, M Vallotton, N Vancheeswaran, R Vincent-Smith, L Visuvanathan, S Vuylsteke, A Waddy, S Wake, R Walden, A Welters, I Whitehouse, T Whittaker, P Whittington, A Papineni, P Wijesinghe, M Williams, M Wilson, L Cole, S Winchester, S Wiselka, M Wolverson, A Wootton, DG Workman, A Yates, B Young, P
Copyright, Publisher and Additional Information:	© 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords:	Phylogenetics; Molecular biology; Immunology; Immune response; Virology
Dates:	Accepted: 22 October 2021 Published (online): 28 October 2021 Published: 19 November 2021
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	11 Jan 2022 18:27
Last Modified:	11 Jan 2022 18:27
Status:	Published
Publisher:	Elsevier BV
Refereed:	Yes
Identification Number:	https://doi.org/10.1016/j.isci.2021.103353
Related URLs:	Author

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

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