Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4+ T cell recognition
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc..
CD4+ T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4+ T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4+ T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4+ T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4+ T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4+ T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4+ T cell immunity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Nature immunology - 23(2022), 12 vom: 02. Dez., Seite 1726-1734 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tye, Emily X C [VerfasserIn] |
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| Links: |
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| Themen: |
Epitopes |
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| Anmerkungen: |
Date Completed 15.12.2022 Date Revised 26.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41590-022-01351-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a CD4+ T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4+ T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4+ T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4+ T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4+ T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4+ T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4+ T cell immunity | ||
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