The School of Biotechnology and Biomolecular Sciences at UNSW

The University of New South Wales

A leading research and teaching school with expertise in biotechnology, molecular biology, genetics, environmental microbiology, medical microbiology, immunology, biochemistry, protein chemistry and other areas of biological science.

Investigation of the Relationship Between IgG4 and IgE Antibodies in Allergic Disease

IgG subclasses have been known for several decades, and subclass responses to specific antigens are routinely reported in the scientific literature. There is some knowledge of how subclass responses are regulated, and there have been many reports that have identified particular subclasses with the response to specific antigens. For example, it is often said that IgG3 antibodies are directed against polysaccharide antigens.

Our overall understanding of IgG subclass functions, however, is poor. We have recently revealed unexpected isotype-specific patterns of somatic point mutations that point to previously unknown relationships between IgE antibodies and other antibodies. We now wish to use this approach to study IgG subclasses. We are particularly interested to compare the mutational patterns of IgE and IgG4 antibodies, for there have been many reports that IgG4 antibodies target allergens. We wish to establish whether or not IgG4 antibodies are clonally related to IgE antibodies through the study of their accumulated somatic point mutations.

This project will involve the development of RT-PCR for the amplification of rearranged VDJ genes from cells that have class switched to IgG4. This may require the development of nested PCRs to amplify the very few transcripts that are likely to be present in samples. PCR products will then be cloned and sequenced. Patterns of mutation will then be determined using bioinformatic tools developed in our laboratory.

BABS personnel that are responsible for this project