BMB Section Seminar: "TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity"
Stian Foss, Inger Sandlie group.
Centre for Immune Regulation (CIR) and Department of Biosciences, University of Oslo, and Department of Immunology, Oslo University Hospital, Rikshospitalet
Figure: TRIM21 inflammatory signaling (Stian Foss).
Antibodies are key molecules in the fight against infections. Although previously thought to mediate protection solely in the extracellular environment, recent research has revealed that antibody-mediated protection extends to the cytosolic compartment of non-hematopoietic cells. This post-entry viral defense mechanism requires binding of the antibody to a cytosolic Fc receptor named tripartite motif containing 21 (TRIM21). In contrast to other Fc receptors, TRIM21 shows remarkably broad isotype specificity as it does not only bind IgG but also IgM and IgA. When viral pathogens coated with these antibody isotypes enter the cytosol, TRIM21 is rapidly recruited and efficient neutralization occurs before the virus has had the time to replicate. In addition, inflammatory signaling is induced. As such, TRIM21 acts as a cytosolic sensor that engages antibodies that have failed to protect against infection in the extracellular environment. We will present data showing how the antiviral properties of human IgG molecules may be modulated by molecular engineering. Such knowledge may guide development of antiviral IgG drugs that are increasingly being evaluated for use in therapy.