Cross- and self-reactivity of allergen molecules from a structural point of view

IgE-mediated cross-reactivity is frequently observed in clinical practice and results from sharing of IgE-binding B cell epitopes by phylogenetically conserved proteins. Cyclophilin, manganese-dependent superoxide dismutase and thioredoxin are clinically tested, cross-reactive pan-allergens. Remarkably, some patients with severe, long-lasting atopic diseases also show cross -reactivity to human homologs of these proteins, indicating that IgE-mediated autoreactivity might play a role in the exacerbation of chronic allergic diseases. The three-dimensional structures of an increasing number of allergens have been solved by X-ray crystallography or NMR spectroscopy. These structures cover a wide variety of different folds and combinations therefore, but no common structural feature determining the allergenicity of a protein could be derived so far from structural information. Although crystal structures do not yet answer the question, why some proteins are allergenic and some others are not, they have strongly contributed to our understanding of cross-reactivity at molecular level. Co-crystallization of an allergen with a bound monoclonal antibody Fab fragment and subsequent solution of the X-ray structure of the complex is the only method allowing the complete definition of a B cell epitope. Alternatively cross-reactive B cell epitopes can be predicted fast and reliably by deter-mining shared features of cross-reactive allergens on sequence and structure level. This knowledge will contribute to reduce the number of molecular structures needed for diagnosis and perhaps immunotherapy of allergic diseases based on recombinant allergens and will help to develop safe and patient-tailored vaccination concepts.