The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells.
de Silva TI., Liu G., Lindsey BB., Dong D., Moore SC., Hsu NS., Shah D., Wellington D., Mentzer AJ., Angyal A., Brown R., Parker MD., Ying Z., Yao X., Turtle L., Dunachie S., COVID-19 Genomics UK (COG-UK) Consortium None., Maini MK., Ogg G., Knight JC., ISARIC4C Investigators None., Peng Y., Rowland-Jones SL., Dong T.
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 recognise 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.