tetano
Editor, Senior Moderator
EMBO J
. 2020 Dec 1;e106228.
doi: 10.15252/embj.2020106228. Online ahead of print.
Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity
Sarah L Caddy[SUP] 1 2 [/SUP], Marina Vaysburd[SUP] 1 [/SUP], Guido Papa[SUP] 1 [/SUP], Mark Wing[SUP] 1 [/SUP], Kevin O'Connell[SUP] 1 [/SUP], Diana Stoycheva[SUP] 3 [/SUP], Stian Foss[SUP] 4 5 [/SUP], Jan Terje Andersen[SUP] 4 5 [/SUP], Annette Oxenius[SUP] 3 [/SUP], Leo C James[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: TRIM21; antibody; non-neutralising; nucleoprotein; virus.
. 2020 Dec 1;e106228.
doi: 10.15252/embj.2020106228. Online ahead of print.
Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity
Sarah L Caddy[SUP] 1 2 [/SUP], Marina Vaysburd[SUP] 1 [/SUP], Guido Papa[SUP] 1 [/SUP], Mark Wing[SUP] 1 [/SUP], Kevin O'Connell[SUP] 1 [/SUP], Diana Stoycheva[SUP] 3 [/SUP], Stian Foss[SUP] 4 5 [/SUP], Jan Terje Andersen[SUP] 4 5 [/SUP], Annette Oxenius[SUP] 3 [/SUP], Leo C James[SUP] 1 [/SUP]
Affiliations
- PMID: 33258165
- DOI: 10.15252/embj.2020106228
Abstract
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.
Keywords: TRIM21; antibody; non-neutralising; nucleoprotein; virus.