Determinants of birch pollen allergenicity

In course of the allergic sensitization process, genetically susceptible individuals become allergic to a certain allergenic source (e.g. pollen allergens), which results in the expression of allergic symptoms upon re-exposure to the source. In case of birch pollen allergy, allergic patients suffer from seasonal hay fever and even from allergic asthma, influencing their quality of life enormously. The induction of symptoms is caused by proteins found in the pollen, called allergens. One protein in birch pollen, named Bet v 1, is of particular interest since over 95% of all birch pollen allergic patients respond to it. Although the mechanism by which allergens trigger symptoms is well understood (effector phase), less is known regarding the initiation of the allergic response (sensitization phase). It appears that the sensitization is triggered by yet-unidentified pollen compounds rather than by the allergens themselves, which seem to play only a secondary role. Therefore, the primary goal of this project is to dissect the pollen source on a molecular level, to characterize essential pollen compounds and to evaluate their contribution in allergic sensitization. Human and murine epithelial and dendritic cells, two major cell types involved in the sensitization process, will be stimulated with the pollen compounds and compared to the effects caused by a complete, untreated birch pollen extract. In mouse models, the effects of the birch pollen compounds will further be studied regarding their capacity to promote allergic sensitization. By combining human and murine experimental models, we expect to identify birch pollen compounds and immunological pathways that help in understanding the mechanism of allergic sensitization. The generated findings as well as the newly gained mechanistic knowledge will pave the way for the development of prophylactic and therapeutic approaches, which might prevent allergies to birch pollen in the future.