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

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posted on 2023-08-02, 09:42 authored by TI de Silva, G Liu, BB Lindsey, D Dong, SC Moore, NS Hsu, D Shah, D Wellington, AJ Mentzer, A Angyal, R Brown, MD Parker, Z Ying, X Yao, L Turtle, S Dunachie, DM Aanensen, K Abudahab, H Adams, A Adams, S Afifi, D Aggarwal, SSY Ahmad, L Aigrain, A Alcolea-Medina, NF Alikhan, E Allara, R Amato, T Annett, S Aplin, CV Ariani, H Asad, A Ash, P Ashfield, F Ashford, L Atkinson, SW Attwood, C Auckland, A Aydin, DJ Baker, P Baker, CE Balcazar, J Ball, JC Barrett, M Barrow, E Barton, M Bashton, AR Bassett, R Batra, C Baxter, N Bayzid, C Beaver, AH Beckett, SM Beckwith, L Bedford, R Beer, A Beggs, KL Bellis, L Berry, B Bertolusso, A Best, E Betteridge, D Bibby, K Bicknell, D Binns, A Birchley, PW Bird, C Bishop, R Blacow, V Blakey, B Blane, F Bolt, J Bonfield, S Bonner, D Bonsall, T Boswell, A Bosworth, Y Bourgeois, O Boyd, DT Bradley, C Breen, C Bresner, J Breuer, S Bridgett, IF Bronner, E Brooks, A Broos, JR Brown, G Bucca, SL Buchan, D Buck, M Bull, PJ Burns, S Burton-Fanning, T Byaruhanga, M Byott, S Campbell, AM Carabelli, JS Cargill, M Carlile
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.

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  • Published

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  • Published version

Journal

iScience

ISSN

2589-0042

Publisher

Elsevier BV

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External DOI

Issue

11

Volume

24

Article number

ARTN 103353

Department affiliated with

  • Global Health and Infection Publications
  • BSMS Publications

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  • Yes

Peer reviewed?

  • Yes

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    Keywords

    Immune responseImmunologyMolecular biologyPhylogeneticsVirologyCOVID-19 Genomics UK (COG-UK) ConsortiumISARIC4C InvestigatorsBiodefenseEmerging Infectious DiseasesClinical ResearchImmunizationInfectious DiseasesVaccine RelatedPrevention3 Good Health and Well Being

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    CC BY 4.0

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