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

The COVID-19 Genomics UK (COG-UK) Consortium, ISARIC4C Investigators, 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, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Matthew Bashton, Clare M. McCannAndrew Nelson, Darren L. Smith, Wen C. Yew, Gregory R. Young

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number103353
Number of pages16
JournaliScience
Volume24
Issue number11
Early online date28 Oct 2021
DOIs
Publication statusPublished - 19 Nov 2021

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