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

COVID-19 Genomics UK Consortium; Anna Mantzouratou

doi:10.1016/j.isci.2021.103353

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

COVID-19 Genomics UK Consortium
, Anna Mantzouratou

Bournemouth University

Research output: Contribution to journal › Article › peer-review

Abstract

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 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 language	English
Article number	103353
Journal	iScience
Volume	24
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2021.103353
Publication status	Published - 19 Nov 2021
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1016/j.isci.2021.103353

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title = "The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.",

abstract = "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 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.",

author = "TI, \{de Silva\} and G Liu and Lindsey BB and \{COVID-19 Genomics UK Consortium\} and D Dong and Moore SC and Hsu NS and D Shah and D Wellington and Mentzer AJ and A Angyal and Rebecca Brown and Parker MD and Z Ying and X Yao and L Turtle and T Dong and Anna Mantzouratou",

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month = nov,

day = "19",

doi = "10.1016/j.isci.2021.103353",

language = "English",

volume = "24",

journal = "iScience",

issn = "2589-0042",

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T1 - The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

AU - TI, de Silva

AU - Liu, G

AU - BB, Lindsey

AU - COVID-19 Genomics UK Consortium

AU - Dong, D

AU - SC, Moore

AU - NS, Hsu

AU - Shah, D

AU - Wellington, D

AU - AJ, Mentzer

AU - Angyal, A

AU - Brown, Rebecca

AU - MD, Parker

AU - Ying, Z

AU - Yao, X

AU - Turtle, L

AU - Dong, T

AU - Mantzouratou, Anna

PY - 2021/11/19

Y1 - 2021/11/19

N2 - 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 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.

AB - 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 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.

UR - http://europepmc.org/abstract/med/34729465

U2 - 10.1016/j.isci.2021.103353

DO - 10.1016/j.isci.2021.103353

M3 - Article

C2 - 34729465

SN - 2589-0042

VL - 24

JO - iScience

JF - iScience

IS - 11

M1 - 103353

ER -

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

Abstract

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