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Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity
Nucleoprotein (N) is an immunodominant antigen in many enveloped virus infections. While the diagnostic value of anti‐N antibodies is clear, their role in immunity is not. This is because while they are non‐neutralising, they somehow clear infection by coronavirus, influenza and LCMV in vivo. Here,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917548/ https://www.ncbi.nlm.nih.gov/pubmed/33258165 http://dx.doi.org/10.15252/embj.2020106228 |
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author | Caddy, Sarah L Vaysburd, Marina Papa, Guido Wing, Mark O’Connell, Kevin Stoycheva, Diana Foss, Stian Terje Andersen, Jan Oxenius, Annette James, Leo C |
author_facet | Caddy, Sarah L Vaysburd, Marina Papa, Guido Wing, Mark O’Connell, Kevin Stoycheva, Diana Foss, Stian Terje Andersen, Jan Oxenius, Annette James, Leo C |
author_sort | Caddy, Sarah L |
collection | PubMed |
description | Nucleoprotein (N) is an immunodominant antigen in many enveloped virus infections. While the diagnostic value of anti‐N antibodies is clear, their role in immunity is not. This is because while they are non‐neutralising, they somehow clear infection by coronavirus, influenza and LCMV in vivo. Here, we show that anti‐N immune protection is mediated by the cytosolic Fc receptor and E3 ubiquitin ligase TRIM21. Exploiting LCMV as a model system, we demonstrate that TRIM21 uses anti‐N antibodies to target N for cytosolic degradation and generate cytotoxic T cells (CTLs) against N peptide. These CTLs rapidly eliminate N‐peptide‐displaying cells and drive efficient viral clearance. These results reveal a new mechanism of immune synergy between antibodies and T cells and highlights N as an important vaccine target. |
format | Online Article Text |
id | pubmed-7917548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79175482021-03-05 Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity Caddy, Sarah L Vaysburd, Marina Papa, Guido Wing, Mark O’Connell, Kevin Stoycheva, Diana Foss, Stian Terje Andersen, Jan Oxenius, Annette James, Leo C EMBO J Articles Nucleoprotein (N) is an immunodominant antigen in many enveloped virus infections. While the diagnostic value of anti‐N antibodies is clear, their role in immunity is not. This is because while they are non‐neutralising, they somehow clear infection by coronavirus, influenza and LCMV in vivo. Here, we show that anti‐N immune protection is mediated by the cytosolic Fc receptor and E3 ubiquitin ligase TRIM21. Exploiting LCMV as a model system, we demonstrate that TRIM21 uses anti‐N antibodies to target N for cytosolic degradation and generate cytotoxic T cells (CTLs) against N peptide. These CTLs rapidly eliminate N‐peptide‐displaying cells and drive efficient viral clearance. These results reveal a new mechanism of immune synergy between antibodies and T cells and highlights N as an important vaccine target. John Wiley and Sons Inc. 2020-12-01 2021-03-01 /pmc/articles/PMC7917548/ /pubmed/33258165 http://dx.doi.org/10.15252/embj.2020106228 Text en © 2020 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Caddy, Sarah L Vaysburd, Marina Papa, Guido Wing, Mark O’Connell, Kevin Stoycheva, Diana Foss, Stian Terje Andersen, Jan Oxenius, Annette James, Leo C Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity |
title | Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity |
title_full | Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity |
title_fullStr | Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity |
title_full_unstemmed | Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity |
title_short | Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity |
title_sort | viral nucleoprotein antibodies activate trim21 and induce t cell immunity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917548/ https://www.ncbi.nlm.nih.gov/pubmed/33258165 http://dx.doi.org/10.15252/embj.2020106228 |
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