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The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
Lim, Wei Shen
Lim, Wei Shen
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-gamma 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. Copyright © 2021 The Author(s).
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2021
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de Silva, T.I., Liu, G., Lindsey, B.B., Dong, D., Moore, S.C., Hsu, N.S., Shah, D., Wellington, D., Mentzer, A.J., Angyal, A., Brown, R., Parker, M.D., Ying, Z., Yao, X., Turtle, L., Dunachie, S., Maini, M.K., Ogg, G., Knight, J.C., Peng, Y., ISARIC4C Investigators, Rowland-Jones, S.L. and Dong, T. (2021) 'The impact of viral mutations on recognition by SARS-CoV-2 specific T cells', iScience, 24(11), pp. 103353. doi: 10.1016/j.isci.2021.103353 https://doi.org/10.1016/j.isci.2021.103353.
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Wei Shen Lim is an ISARIC4C Investigator.