Unravelling the distinct biological activities of the four industrially- and medically-important human IgG1-IgG4 antibody subclasses

The different antibody hinges at the centre of the human IgG1, IgG2, IgG3 and IgG4 subclasses are key to their very different reactivities, such as binding to their Fc receptors. A molecular understanding of these marked molecular differences between the subclasses is key for understanding major applications of the human antibodies as pharmaceuticals, as well as the role of IgG in disease. We have an extensive background in the atomistic modelling of IgG1, IgG2 and IgG4 antibodies. We have obtained very clean preparations of polyclonal and myeloma human IgG3, and have high quality X-ray scattering data on this. By performing neutron scattering of these IgG3 and their deglycosylated forms, and submitting the scattering curves to atomistic modelling, we will identify the solution structures of this important subclass and how its stability is affected by glycans.