Many forms of inhalant allergy are associated with food allergy due to cross-reactivity between inhalant allergens and homologous food allergens. For instance, about 70% of birch pollen allergic patients show adverse reactions to fruits, nuts and vegetables such as apple, hazelnut, kiwi fruit, stone fruits, celery and many more. However, most patients react to only a limited number of these foods and some patients even do not show any symptoms of food allergy despite being sensitized to the cross-reactive major birch pollen allergen, Bet v 1.
The hypothesis underlying this FWF-funded project is that the epitope recognition profile of Bet v 1-specific IgE determines the clinical consequences of Bet v 1 sensitization. Thus, we aim to characterize IgE epitopes of Bet v 1 and its homologues from plant foods and compare IgE binding to these epitopes with clinical symptoms in a large sample of well-characterized birch pollen allergic patients.
Comparison of the molecular surfaces of Bet v 1-related allergens. Conserved (yellow) and variable residues (blue) are mapped onto the surface of Bet v 1 [PDB:1bv1]. The depicted allergens are from apple (Mal d 1), soybean (Gly m 4) and celeriac (Api g 1).
Allergenicity of tropomyosins correlated with their similarities to human homologues. Non-allergenic vertebrate tropomyosins (black) show high sequence identities to human tropomyosins, while sequences of allergenic invertebrate tropomyosins (red) diverge from their human homologues by at least 40%.
One of the many unresolved problems in allergy research is the question what makes a protein allergenic. Besides examining the behaviour of immune cells or model animals upon contact with allergenic and non-allergenic proteins, the availability of large allergen databases in combination with sequence, structure and protein family data now enables researchers to use sequence and structural analysis to gain new insights and lay the basis for novel experimental approaches.
Members of the Biochemistry and Bioinformatics group aim at answering some of the following questions. What is the distribution of allergenic and non-allergenic proteins within allergen containing protein families? Which sequence-related factors, such as similarity to human homologues, similarity to parasite or bacterial proteins or overall sequence conservation with a protein family, show a connection to allergenicity? Can IgE cross-reactivity between homologous allergens be predicted based on sequence similarity data?
Protein famiies that contain the highest numbers of allegens as retrieved from the AllFam database..
In recent years, it became clear that most allergenic proteins can be classified into an astonishingly small number of families. Members of these protein families possess similar structures and, in many cases, also similar biochemical functions. This led to the hypothesis that allergenicity depends on structural or functional characteristics of proteins. In addition, common protein family membership is a prerequisite of IgE and T cell cross-reactivity.
In order to help researchers and clinicians getting an overview of families of allergens and their allergenic members, we developed the AllFam allergen family database, a Web resource that enables the user to get protein family data for a frequently updated set of allergens derived from the Allergome database.
Allergens are distributed into few protein families and possess a restricted number of biochemical functions.
J Allergy Clin Immunol 2008, 121, 847-52. [PubMed]