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Cambridge Immunology Network



Antibodies have the ability to recognise and bind an almost limitless diversity of molecular conformations, permitting the specific identification of pathogens. The intracellular environment is usually free of antibody, but we have recently demonstrated that pathogens can bring antibodies into the cell during infection. Intracellular antibody is recognised by a high affinity Fc receptor, TRIM21 which promotes the rapid neutralisation of viruses and initiates inflammatory signalling pathways. This system is highly efficient and explains the long-standing observation that a single antibody is able to neutralise a virus particle, which is approximately 1,000 times its molecular mass . In this way, the intracellular environment is protected by the huge diversity of antibodies using a single receptor. Our research aims to understand the role of intracellular antibody detection in the natural immune response and devise novel strategies to enhance immunity.




Key publications: 

Intracellular sensing of complement C3 activates cell autonomous immunity (2014) Jerry C. H. Tam, Susanna R. Bidgood, William A. McEwan, Leo C. James Science  2014: Vol. 345 no. 6201

McEwan WA, Tam JC, Watkinson RE, Bidgood SR, Mallery DL, James LC. Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21. Nat Immunol. 2013 Apr;14(4):327-36.

McEwan WA, Hauler F, Williams CR, Bidgood SR, Mallery DL, Crowther RA, James LC. Regulation of virus neutralization and the persistent fraction by TRIM21. J Virol. 2012 Aug;86(16):8482-91.
Hauler F, Mallery DL, McEwan WA, Bidgood SR, James LC. AAA ATPase p97/VCP is essential for TRIM21-mediated virus neutralization. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19733-8.
Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC. Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nat Struct Mol Biol. 2012 Mar 11;19(4):411-6.
McEwan WA, Mallery DL, Rhodes DA, Trowsdale J, James LC. Intracellular antibody-mediated immunity and the role of TRIM21. Bioessays. 2011 Nov;33(11):803-9.
Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19985-90
Dr William  McEwan
Not available for consultancy


Departments and institutes: 
Person keywords: 
intracellular immunity