The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)
Open accessAbstract
Antibodies provide effective antiviral immunity despite the fact that viruses escape into cells when they infect. Here we show that antibodies remain attached to viruses after cell infection and mediate an intracellular immune response that disables virions in the cytosol. We have discovered that cells possess a cytosolic IgG receptor, tripartite motif-containing 21 (TRIM21), which binds to antibodies with a higher affinity than any other IgG receptor in the human body. TRIM21 rapidly recruits to incoming antibody-bound virus and targets it to the proteasome via its E3 ubiquitin ligase activity. Proteasomal targeting leads to rapid degradation of virions in the cytosol before translation of virally encoded genes. Infection experiments demonstrate that at physiological antibody concentrations TRIM21 neutralizes viral infection. These results reveal an intracellular arm of adaptive immunity in which the protection mediated by antibodies does not end at the cell membrane but continues inside the cell to provide a last line of defense against infection.
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Cites
Pathogen Recognition and Innate Immunity
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Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function
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“Recently we described an intracellular cytosolic protein called tripartite motif-containing 21 (TRIM21) that is capable of binding to an invariant region of antibody molecules via its PRYSPRY domain (4).”
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Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains
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TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved
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Retroviral Restriction Factor TRIM5α Is a Trimer
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Cited by
IgG Subclasses and Allotypes: From Structure to Effector Functions
Vidarsson, G., Dekkers, G., & Rispens, T. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00520 · Cited by 2,667
Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins
Yang, N. J., & Hinner, M. J. (2015) · Methods in Molecular Biology · doi:10.1007/978-1-4939-2272-7_3 · Cited by 826
The function of Fcγ receptors in dendritic cells and macrophages
Guilliams, M., Bruhns, P., Saeys, Y., Hammad, H., & Lambrecht, B. N. (2014) · Nature Reviews Immunology · doi:10.1038/nri3582 · Cited by 639
Mouse and human FcR effector functions
Bruhns, P., & Jönsson, F. (2015) · Immunological Reviews · doi:10.1111/imr.12350 · Cited by 579
Interferon-inducible effector mechanisms in cell-autonomous immunity
MacMicking, J. D. (2012) · Nature Reviews Immunology · doi:10.1038/nri3210 · Cited by 579
Metadata
- Authors
- Mallery, D. L., McEwan, W. A., Bidgood, S. R., Towers, G. J., Johnson, C. M., & James, L. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-11-02
- Volume
- 107
- Issue
- 46
- Pages
- 19985-19990
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2052172534
- Cited by
- 516
- References
- 15
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Mallery, D. L., McEwan, W. A., Bidgood, S. R., Towers, G. J., Johnson, C. M., & James, L. C. (2010). Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1014074107
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