Allergen mimotopes for 3-dimensional epitope search and induction of antibodies inhibiting human IgE

There is no definite information available on the structural characteristic s of IgE binding epitopes on allergenic molecules, although it is widely ac cepted that most of them are conformational. In the current study we aimed to characterize the IgE epitope of Bet v 1, the major birch pollen allergen , by the application of phage display peptide libraries. We purified IgE sp ecific for Bet v 1 from allergic patients' sera to select mimotopes represe nting artificial IgE epitopes by biopanning of phage libraries. By linear a lignment, it was not possible to attribute mimotope sequences to the primar y structure of Bet v 1. We developed a computer-aided, S-dimensional coarse -grained epitope search. The 3-dimensional. search, followed by statistical analysis, revealed an exposed area on the Bet v 1 molecule (located betwee n residues 9-22 and 104-123) as the IgE binding structure. The IgE epitope was located at a 30 Angstrom distance from a previously described IgG epito pe and the respective mimotope, designated Bet mim E. Such mimotopes could potentially be used for the induction of IgG capable of interfering with th e IgE/allergen interaction. To test this hypothesis, we immunized BALB/c mi ce with the phage-displayed Bet mim E. Immunizations resulted in the induct ion of Bet v 1-specific IgG, which was able to block the IgE binding to Bet v 1 in vitro. Based on these observations, we propose that immunotherapy w ith IgE mimotopes generated by biopannings result in formation of blocking IgG. We conclude that mimotope immunotherapy may represent a new and promis ing concept for treatment of type I allergic disease.