       Links
       Contact
       Terms - Privacy

Division of Immunopathology
Department of Pathophysiology and Allergy Research
Center of Pathophysiology, Infectiology & Immunology

Medical University of Vienna

Vienna General Hospital, AKH, 3Q
Waehringer Guertel 18-20
A-1090 Vienna, Austria

Molecular approaches to dissect pathomechanisms of allergy [Valenta]

Project summary

In this project we use defined and clinically relevant allergen molecules, recombinant and synthetic allergen derivatives as well as epitopes thereof to study mechanisms of allergic inflammation. IgE recognition of allergens initiates acute allergic manifestations by activation of mast cells and basophils. We have generated and characterized monoclonal IgE antibodies specific for epitopes on major respiratory allergens. Using these tools we plan to investigate whether the geometrical arrangement of epitopes and their affinity for IgE can influence the degranulation reaction. For this purpose we will engineer artifical allergens by grafting epitopes with defined affinities for the corresponding IgE antibodies on structurally well defined scaffolds and test them for induction of basophil/mast cell degranulation.
Given the importance of IgE in allergic inflammation we have engineered a non-anaphylactic, recombinant scFv with high affinity for IgE which prevents IgE-binding to FcepsilonRI and recognizes cell-bound IgE. We plan to characterize the molecular and structural interaction of the scFv with IgE and to study in vitro and in vivo the usefulness of this reagent for the therapeutic targeting of IgE-bearing and secreting cells and eventually the effects of depletion of IgE with the scFv by plasmapheresis from patients.
Using recombinant, non-IgE-reactive but T cell epitope-containing derivatives of the major birch pollen allergen, Bet v 1, we could demonstrate the importance of non-IgE-mediated mechanisms in chronic allergic skin inflammation. We now plan to study the potential of various clinically relevant allergens to induce chronic allergic inflammation, to identify responsible T cell epitopes and study the mechanisms for the T cell-mediated tissue damage. Furthermore, we would like to study whether non-IgE-reactive allergen derivatives can be used for diagnostic purposes to identify allergic patients suffering also from non-IgE-mediated inflammation and ultimately, to develop strategies for the antigen-specific down-modulation of this process.