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Publication : Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity.

First Author  Caddy SL Year  2021
Journal  EMBO J Volume  40
Issue  5 Pages  e106228
PubMed ID  33258165 Mgi Jnum  J:303981
Mgi Id  MGI:6510449 Doi  10.15252/embj.2020106228
Citation  Caddy SL, et al. (2021) Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity. EMBO J 40(5):e106228
abstractText  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.
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