       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

The structural basis for allergenicity [Keller]

Project Summary

The determination of cross-reactive IgE epitopes on allergens is a major challenge. Mapping of sequential IgE epitopes is time consuming, extremely tedious and possible for only few allergens and epitopes. The accurate determination of conformational IgE epitopes recognized by polyclonal patients IgE on the majority of allergens, especially respiratory allergens, is almost impossible. Most structural methods for epitope determination (e.g., co-crystallization, NMR-based hydrogen exchange) work only with monoclonal antibodies and therefore epitopes can only be determined one at the time and never represent the polyclonal situation found in reality.
In the first two periods of the SFB we have determined the structures of highly cross-reactive allergens belonging to the same structural family (two members of the two EF-hand pollen allergen family, and three members of the TLP family). In addition, we were able to obtain new crystal forms of several mite allergens and pollen allergens.
In the final period of the SFB we will pursue the following aims:
1. Using the structures of the cross-reactive allergens and the known structures of non-allergenic homologues we are developing programs to discern cross-reactive from non cross-reactive surface patches. Correlating this structure based information with the immunological data on cross-reactivity will allow us to predict putative IgE and IgG epitopes.
2. The second aim of the project is the structure determination of allergens which have been crystallized in the previous period. In addition, newly emerging allergens from our collaboration partners will be received for crystallization trials and their structures determined. For proteins which are not crystallizable and which are of moderate size, a structure solution by NMR methods will be pursued. We will also continue our efforts to crystallize allergen-antibody complexes using Fab fragments from monoclonal antibodies and specific single-chain antibody fragments (scFv).
3. The third aim will be continued biophysical characterization of native and recombinant allergens using CD spectroscopy, SAXS and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). We will also apply established methods (NMR spectroscopy) to determine the allergen-antibody interaction sites.

For further details goto http://physchem.kfunigraz.ac.at/sb/projects/all.htm