Antibodies are a critical component of immune defence but they provide purely extracellular protection – once inside a cell, a pathogen is safe. This is the view of humoral immunity that has existed for over 100 years. However, recent work in my lab has led to the discovery of a missing system of antibody-mediated immunity that takes place inside infected cells. I have identified a novel cytosolic antibody receptor (TRIM21) that binds to antibody-coated viruses after cellular infection and targets them for degradation in the proteasome. Importantly, TRIM21-mediated immunity is capable of clearing a cell of virus within hours of infection. This discovery represents a paradigm shift in how we think about viral immunity and offers the potential for new types of antiviral drugs.
This grant application outlines key experiments to determine how intracellular antibody immunity works, what it works against and how we can augment or replicate it in the treatment of disease.
Field of science
- /natural sciences/biological sciences/microbiology/virology
Call for proposal
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