Host physiology of the intracellular humoral immune response


  • Dr Leo James

    University of Cambridge

Project summary

Antibodies are a key molecule of the immune response. It was previously thought that they only work extracellularly, but we have shown that antibodies also prevent infection intracellularly.

We want to understand how intracellular antibody immunity works and is regulated. We will investigate TRIM21, the receptor for antibodies carried into the cell by viruses during infection. TRIM21 is widely expressed but in an inactive form. We will combine biophysics with cellular and organismal infection models to understand how TRIM21 is activated. TRIM21 has a unique ability to target viruses inside the cell and strip them of their protective shell. We will investigate whether this makes viruses more susceptible to other immune sensors, such as RIG-I and cGAS. We recently found that complement C3 also prevents infection from inside the cell but in a different way to antibodies. We will identify the receptor that detects C3 and compare its activity with TRIM21. We will also determine which other serum proteins have intracellular functions.

Understanding how these newly identified immune processes work may reveal new therapeutic possibilities and help in the development of future vaccines.