Allergic responses are mediated by immunoglobulin E (IgE) antibodies. IgE contains an extra domain pair at its hinge joining its Fab and Fc regions; its significance is not fully understood. The allergic response involves complexes between IgE and its high and low affinity receptors FcεRI and FcεRII. The PhD project will identify the role of the Fab regions in IgE-receptor complexes. Conformational studies in a broad range of solution conditions will locate the Fab regions of IgE relative to the Fc region. The outcome will help decipher its biological mechanism and is relevant to the >$30 billion antibody biotechnology industry.
Hunt, J., Keeble, A.H., Dale, R.E., Corbett, M.K., Beavil, R.L., Levitt, J., Swann, M.J., Suhling, K., Ameer-Beg, S., Sutton, B.J., Beavil, A.J. (2012) A fluorescent biosensor reveals conformational changes in human immunoglobulin E Fc: Implications for mechanisms of receptor binding, inhibition, and allergen recognition. J. Biol. Chem. 287, 17459-17470.
Rayner, L. E., Kadkhodayi-Kholghi, N., Heenan, R. K., Gor, J., Dalby, P. A. & Perkins S. J. (2013). The solution structure of rabbit IgG accounts for its interactions with the Fc receptor and complement C1q and its conformational stability. J. Mol. Biol. 425, 506-523.
Rayner, L. E., Hui, G. K., Gor, J., Heenan, R. K. Dalby, P. A. & Perkins S. J. (2014) The Fab conformations in the solution structure of human IgG4 restrict access to its Fc region: implications for functional activity. J. Biol. Chem. Submitted for final acceptance.
Perkins, S. J., Okemefuna, A. I., Nan, R., Li, K. & Bonner, A. (2009). Invited review. Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights. J. Roy. Soc. Interface. 6, S679-S696.
Bonner, A., Almogren, A., Furtado, P. B., Kerr, M. A. & Perkins, S. J. (2009). Location of secretory component on the Fc edge of dimeric IgA1 reveals insight into the role of secretory IgA1 in mucosal immunity. Mucosal Immunology (Nature Publishing Group), 2, 74-84.