Recombinant allergen molecules: tools to study effector cell activation

Authors


Correspondence to: Rudolf Valenta
“Molecular Immunopathology Group”
Department of Pathophysiology
University of Vienna Medical School
Vienna General Hospital
Waehringer Guertel 18–20
A-1090 Vienna
Austria
Tel: 43 1 40400 5108
Fax: 43 1 40400 5130
e-mail: Rudolf.Valenta@akh-wien.ac.at

Abstract

Summary: The IgE antibody-mediated activation of allergic effector cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect effector cell activation. If the structural requirements for effector cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects.

The authors would like to thank Dr. Peter Valent, Department of Hematology, Vienna General Hospital, Austria, and Dr. Steven C. Almo, Department of Biochemistry, Albert Einstein College of Medicine, New York, USA, for fruitful collaboration regarding effector cell activation and structural biology, respectively. The skilful editorial assistance of Irmgard Lubelik is acknowledged. This work was supported by grant Y078 GEN of the Austrian Science Fund and by the ICP Program of the Austrian Federal Ministry for Education, Science and Culture.

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