Mechanisms of food allergies

To date little is known about basic mechanisms in the sensitization and effector phase of food allergy. Knowledge about underlying mechanisms is crucial for prevention strategies of sensitization and for the development of specific therapies. The overall aim of the present study is, therefore, to identify the cells responsible for antigen handling during the induction and effector phase of the disease using an oral immunization protocol in different murine knock-out models. The first aim of the project will be to elucidate the site of the protein uptake in the gastrointestinal tract and to investigate cellular interactions in antigen processing and presentation. The second part of the study will focus on analyzing the role of classical T helper cells in food allergy induction. We have previously observed that the three dimensional structure of proteins plays a critical role for their allergenicity. Consequently, the working hypothesis in this part of the project is that cells recognizing conformation play a key role in sensitization. After immunization experiments in STAT6 and IL-13 deficient mice, cytokine and antibody profiles will elucidate interactions between T cell subsets and B cells. The third goal is to investigate the role of eosinophils in the establishment and exacerbation of clinically manifest food allergy using eotaxin/IL-5 knock-outs compared to wildtype mice. The applicant plans to use the previously established immunization protocol (antigen feedings under acid-suppression) and to compare the extent and quality of induced immune responses upon allergen challenge. It is anticipated that this study will provide novel information about the sensitizing process, as well as about the effector cells responsible for clinical reactions after ingestion of dietary compounds in IgE mediated food allergy. Thus, we expect that the results of our study may be translated into practical recommendations for dietary habits or for the food processing industry.