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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Main Authors: 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, Maini, MK, Ogg, G, Knight, JC, Peng, Y, Rowland-Jones, SL, Dong, T
Format: Journal article
Language:English
Published: Cell Press 2021
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author 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
Maini, MK
Ogg, G
Knight, JC
Peng, Y
Rowland-Jones, SL
Dong, T
author_facet 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
Maini, MK
Ogg, G
Knight, JC
Peng, Y
Rowland-Jones, SL
Dong, T
author_sort de Silva, TI
collection OXFORD
description 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.
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spelling oxford-uuid:54ffc1a5-c731-4cab-aa89-b3699df2dda22022-03-26T16:41:19ZThe impact of viral mutations on recognition by SARS-CoV-2 specific T-cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:54ffc1a5-c731-4cab-aa89-b3699df2dda2EnglishSymplectic ElementsCell Press2021de Silva, TILiu, GLindsey, BBDong, DMoore, SCHsu, NSShah, DWellington, DMentzer, AJAngyal, ABrown, RParker, MDYing, ZYao, XTurtle, LDunachie, SMaini, MKOgg, GKnight, JCPeng, YRowland-Jones, SLDong, TWe 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.
spellingShingle 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
Maini, MK
Ogg, G
Knight, JC
Peng, Y
Rowland-Jones, SL
Dong, T
The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells
title The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells
title_full The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells
title_fullStr The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells
title_full_unstemmed The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells
title_short The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells
title_sort impact of viral mutations on recognition by sars cov 2 specific t cells
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