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

Thushan I de Silva ; Guihai Liu ; Benjamin B Lindsey ; Danning Dong ; Shona C Moore ; Nienyun Sharon Hsu ; Dhruv Shah ; Dannielle Wellington ; Alexander J Mentzer ; Adrienn Angyal ; +14 more... Rebecca Brown ; Matthew D Parker ; Zixi Ying ; Xuan Yao ; Lance Turtle ; Susanna Dunachie ; COVID-19 Genomics UK (COG-UK) Consortium ; Mala K Maini ; Graham Ogg ; Julian C Knight ; ISARIC4C Investigators ; Yanchun Peng ; Sarah L Rowland-Jones ; Tao Dong ; (2021) The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24 (11). 103353-. ISSN 2589-0042 DOI: 10.1016/j.isci.2021.103353
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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.
Item Type Article
Elements ID 167283
Date Deposited 23 Nov 2021 20:00

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