Abstract

Intracellular Antibody Immunity and the Cytosolic Fc Receptor TRIM21

Leo James, , MRC Laboratory of Molecular Biology

TRIM21 is a recently discovered mammalian Fc receptor and E3 ubiquitin ligase expressed in the cytosol of most cells. It is the highest affinity IgG receptor in man and has the widest known antibody specificity, being capable of also binding IgM and IgA. TRIM21 mediates an intracellular humoral response that protects against antibody-opsonized pathogens that invade the cytosol during infection. Upon detection, TRIM21 activates key immune transcription pathways to induce a potent antiviral state. Simultaneous with and independent of immune activation, TRIM21 recruits cellular degradation machinery, which catalyse the disassembly and destruction of the virion to prevent its replication. These dual sensor and effector functions are made possible by a system of tightly regulated ubiquitination and deubiquitination events. TRIM21 also integrates with other cytosolic sensors such as RIG-I and cGAS to promote a rapid antiviral response. Initially shown to protect against nonself pathogens, recent data suggests that TRIM21 may also be effective against pathogenic self-aggregates such as the prion-like neurodegenerative protein tau.