The European rabbit IgA's as a model for therapeutic antibodies development: a genomic and functional approach.

With 13 IgA subclasses the European rabbit (Oryctolagus cuniculus) has the most complex IgA system of all studied mammals. Moreover, our studies of three wild rabbits have revealed six additional copies of rabbit IgA genes. Additionally, the rabbit has lost FcalphaRI, the prototypic IgA FcR, and hence rabbit IgA's must use alternative receptors. This makes the European rabbit an incomparable source of IgA's natural variation coupled to the fact that uncovering which FcR's are used may contribute to finding valuable alternative pathways. With this project we plan to i) characterize the genetic diversity of European rabbit IgA, ii) identify which FcR's are used by rabbit IgA subclasses, and iii) explore the functional capabilities of selected rabbit IgA subclasses and of engineered human IgG and IgA incorporating selected rabbit hinge sequences.