Antibodies are a key component of the adaptive immune response but their activity has previously thought to be limited to the extracellular environment. We have demonstrated that pathogens traffic surface-bound antibodies to the intracellular compartment where they are recognised and neutralized by the high affinity cytosolic Fc receptor TRIM21. In this study we demonstrate that following detection of pathogen-antibody complexes, TRIM21 is able to synthesise K63-linked ubiquitin chains resulting in signalling via NF-κB, AP-1 and IRF3/5/7 pathways. Detection by TRIM21 is sufficient to induce the production of cytokines including CXCL10, IL-6 and IFN-β. Furthermore a wide range of intracellular pathogens, including Salmonella, non-enveloped DNA viruses and RNA viruses can be detected by TRIM21. TRIM21 therefore provides context-dependent detection of intracellular antibody, mediating potent neutralization and signalling functions.
- Copyright © 2013 by The American Association of Immunologists, Inc.