학술논문
The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
Document Type
article
Author
de Silva, Thushan I; Liu, Guihai; Lindsey, Benjamin B; Dong, Danning; Moore, Shona C; Hsu, Nienyun Sharon; Shah, Dhruv; Wellington, Dannielle; Mentzer, Alexander J; Angyal, Adrienn; Brown, Rebecca; Parker, Matthew D; Ying, Zixi; Yao, Xuan; Turtle, Lance; Dunachie, Susanna; Aanensen, David M; Abudahab, Khalil; Adams, Helen; Adams, Alexander; Afifi, Safiah; Aggarwal, Dinesh; Ahmad, Shazaad SY; Aigrain, Louise; Alcolea-Medina, Adela; Alikhan, Nabil-Fareed; Allara, Elias; Amato, Roberto; Annett, Tara; Aplin, Stephen; Ariani, Cristina V; Asad, Hibo; Ash, Amy; Ashfield, Paula; Ashford, Fiona; Atkinson, Laura; Attwood, Stephen W; Auckland, Cressida; Aydin, Alp; Baker, David J; Baker, Paul; Balcazar, Carlos E; Ball, Jonathan; Barrett, Jeffrey C; Barrow, Magdalena; Barton, Edward; Bashton, Matthew; Bassett, Andrew R; Batra, Rahul; Baxter, Chris; Bayzid, Nadua; Beaver, Charlotte; Beckett, Angela H; Beckwith, Shaun M; Bedford, Luke; Beer, Robert; Beggs, Andrew; Bellis, Katherine L; Berry, Louise; Bertolusso, Beatrice; Best, Angus; Betteridge, Emma; Bibby, David; Bicknell, Kelly; Binns, Debbie; Birchley, Alec; Bird, Paul W; Bishop, Chloe; Blacow, Rachel; Blakey, Victoria; Blane, Beth; Bolt, Frances; Bonfield, James; Bonner, Stephen; Bonsall, David; Boswell, Tim; Bosworth, Andrew; Bourgeois, Yann; Boyd, Olivia; Bradley, Declan T; Breen, Cassie; Bresner, Catherine; Breuer, Judith; Bridgett, Stephen; Bronner, Iraad F; Brooks, Ellena; Broos, Alice; Brown, Julianne R; Bucca, Giselda; Buchan, Sarah L; Buck, David; Bull, Matthew; Burns, Phillipa J; Burton-Fanning, Shirelle; Byaruhanga, Timothy; Byott, Matthew; Campbell, Sharon; Carabelli, Alessandro M; Cargill, James S; Carlile, Matthew
Source
iScience. 24(11)
Subject
Language
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.