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

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., COVID-19 Genomics UK (COG-UK) Consortium, , Maini, M. K., Ogg, G., Knight, J. C., ISARIC4C Investigators, , Peng, Y., 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), 103353.

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DOI: 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.

Item Type:Article
ISSN:2589-0042
Group:Faculty of Science & Technology
ID Code:36742
Deposited By: Symplectic RT2
Deposited On:15 Mar 2022 13:24
Last Modified:15 Mar 2022 13:24

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