Summary 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. Graphical abstract Highlights • Amino acid variants in dominant SARS-CoV-2 T cell epitopes result in recognition loss • CD8+ clones with diverse T cell receptor repertoires fail to recognize variant epitopes • Ongoing surveillance for SARS-CoV-2 variants resulting in T cell evasion is important Phylogenetics; Molecular biology; Immunology; Immune response; Virology
【저자키워드】 immunology, immune response, Virology, Molecular biology, phylogenetics, 【초록키워드】 SARS-CoV-2, variant, SARS-CoV-2 variant, Humoral immunity, Surveillance, ORF3a, nucleocapsid, Lineage, receptor, epitope, IFN-γ, Amino acid, Abstract, sequence, CD8+, clone, killing, dominant, highlight, resulting, identify, assays, recognize, 【제목키워드】 SARS-CoV-2, viral mutation,