• Sabine Flicker, Peter Steinberger, Tanja Ball, Maria-Theresa Krauth, Petra Verdino, Peter Valent, Steve Almo, and Rudolf Valenta.
• Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria.
• J. Allergy Clin. Immunol. 2006 Jun 1; 117 (6): 1336-43.

BackgroundThe major timothy grass pollen allergen Phl p 1 is one of the most potent and frequently recognized environmental allergens.ObjectiveWe sought to study at a molecular and structural level the IgE recognition of Phl p 1 and its relation to allergenic activity.MethodsMonoclonal human IgE antibody fragments specific for Phl p 1 and group 1 allergens from various grasses were isolated from a combinatorial library made of lymphocytes from patients with grass pollen allergy. Recombinant Phl p 1 fragments and the 3-dimensional structure of Phl p 1 were used to localize the major binding site for the IgE antibodies. A rPhl p 1 fragment containing this binding site was expressed in Escherichia coli, purified, and tested for IgE reactivity and allergenic activity with sera and basophils from patients with grass pollen allergy.ResultsMonoclonal antibodies, as well as polyclonal serum IgE, from patients with grass pollen allergy defined a C-terminal fragment of Phl p 1 that represents a sterically oriented portion on the Phl p 1 structure. This Phl p 1 portion bound most of the allergen-specific IgE antibodies and contained the majority of the allergenic activity of Phl p 1.ConclusionIgE recognition of spatially clustered epitopes on allergens might be a general factor determining their allergenic activity.Clinical ImplicationsGeographic distribution of IgE epitopes on an allergen might influence its allergenic activity and hence explain discrepancies between diagnostic test results based on IgE serology and provocation testing. It might also form a basis for the development of low allergenic vaccines.

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