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

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de Silva, TI, Liu, G, Lindsey, BB ORCID: 0000-0003-4227-2592, Dong, D, Moore, SC ORCID: 0000-0001-8610-2806, Hsu, NS ORCID: 0000-0003-2356-9155, Shah, D ORCID: 0000-0002-6198-8273, Wellington, D ORCID: 0000-0002-9277-0306, Mentzer, AJ ORCID: 0000-0002-4502-2209, Angyal, A et al (show 90 more authors) , Brown, R, Parker, MD, Ying, Z, Yao, X, Turtle, L ORCID: 0000-0002-0778-1693, Dunachie, S, Aanensen, DM, Abudahab, K, Adams, H, Adams, A, Afifi, S, Aggarwal, D, Ahmad, SSY, Aigrain, L, Alcolea-Medina, A, Alikhan, NF, 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 and Carlile, M (2021) The impact of viral mutations on recognition by SARS-CoV-2 specific T cells Iscience, 24 (11). 103353-. ISSN 2589-0042, 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 FTSDYYQLY<inf>207-215</inf>; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF<inf>9-17</inf>; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK<inf>361-369</inf>. 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:	Source info: CELL-REPORTS-D-21-02019
Uncontrolled Keywords:	COVID-19 Genomics UK (COG-UK) Consortium, ISARIC4C Investigators
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	18 Nov 2021 15:07
Last Modified:	22 Jan 2026 08:56
DOI:	10.1016/j.isci.2021.103353
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3143428
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