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

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; +14 more... Brown, Rebecca; Parker, Matthew D; Ying, Zixi; Yao, Xuan; Turtle, Lance; Dunachie, Susanna; COVID-19 Genomics UK (COG-UK) Consortium; Maini, Mala K; Ogg, Graham; Knight, Julian C; ISARIC4C Investigators; Peng, Yanchun; Rowland-Jones, Sarah L; Dong, Tao; (2021) The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience, 24 (11). 103353-. ISSN 2589-0042 DOI: https://doi.org/10.1016/j.isci.2021.103353

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.

Additional Information

Item Type	Article
Faculty and Department	Faculty of Infectious and Tropical Diseases > Department of Infection Biology
Research Centre	Covid-19 Research
PubMed ID	34729465
Elements ID	167283