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B cell epitopes of the major timothy grass pollen allergen, Phl p 1, revealed by gene fragmentation as candidates for immunotherapy

TANJA BALL^*, THOMAS FUCHS, WOLFGANG R. SPERR^§, PETER VALENT^§, LUCA VANGELISTA, DIETRICH KRAFT^* and RUDOLF VALENTA^*1

^* Division of Immunopathology, Department of General and Experimental Pathology, AKH, University of Vienna, Austria;
Department of Dermatology, Georg August University Göttingen, Germany;
^§ Department of Internal Medicine I, Division of Hematology and Hemostaseology, AKH, University of Vienna, Austria; and Structural Biology Programme, EMBL, Heidelberg, Germany

¹Correspondence: Molecular Immunopathology Group, Department of General and Experimental Pathology, AKH, University of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria. E-mail: A5311daa{at}awiuni11.edvz.univie.ac.at

Group 1 grass pollen allergens are recognized by IgE antibodies of almost 40% of allergic individuals and therefore belong to the most important elicitors of Type I allergy worldwide. We have previously isolated the cDNA coding for the group 1 allergen from timothy grass, Phl p 1, and demonstrated that recombinant Phl p 1 contains most of the B cell as well as T cell epitopes of group 1 allergens from a variety of grass and corn species. Here we determine continuous B cell epitopes of Phl p 1 by gene fragmentation. IgE antibodies of grass pollen allergic patients identified five continuous epitope-containing areas that on an average bound 40% of Phl p 1-specific IgE antibodies and were stably recognized in the course of disease. In contrast to untreated patients, patients undergoing grass pollen immunotherapy started to mount IgG₄ antibodies to the recombinant IgE-defined fragments in the course of immunotherapy. The protective role of these IgG₄ antibodies is demonstrated by observations that 1) increases in rPhl p 1 fragment-specific IgG₄ were in parallel with decreases in Phl p 1-specific IgE, and 2) preincubation of rPhl p 1 with patients sera containing rPhl p 1 fragment-specific IgG₄ blocked histamine release from basophils of an untreated grass pollen allergic patient. We propose to use recombinant Phl p 1 fragments for active immunotherapy in order to induce protective IgG responses against IgE epitopes in grass pollen allergic patients. This concept may be applied for the development of allergy vaccines whenever the primary sequence or structure of an allergen is available.—Ball, T., Fuchs, T., Sperr, W. R., Valent, P., Vangelista, L., Kraft, D., Valenta, R. B cell epitopes of the major timothy grass pollen allergen, Phl p 1, revealed by gene fragmentation as candidates for immunotherapy.

Key Words: Type I allergy • allergen gene fragmentation • immunotherapy • blocking antibodies

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