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2021-1-20 3:20:11

Caddy SL, Vaysburd M, Papa G, Wing M, O´Conn. Viral nucleoprotein antibodies activate TRIM21 and induce T cell immunity. EMBO J. 2020 Dec 1:e106228
submited by kickingbird at Dec, 2, 2020 10:22 AM from EMBO J. 2020 Dec 1:e106228

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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