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

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...

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Detalles Bibliográficos
Autores principales: 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, Brown, Rebecca, Parker, Matthew D., Ying, Zixi, Yao, Xuan, Turtle, Lance, Dunachie, Susanna, Maini, Mala K., Ogg, Graham, Knight, Julian C., Peng, Yanchun, Rowland-Jones, Sarah L., Dong, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552693/
https://www.ncbi.nlm.nih.gov/pubmed/34729465
http://dx.doi.org/10.1016/j.isci.2021.103353
Descripción
Sumario: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 FTSDYYQLY(207-215); due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF(9-17); and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK(361-369). 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.