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Peptide mimotopes displayed by phage inhibit antibody binding to Bet v 1, the major birch pollen allergen, and induce specific IgG response in mice

^a Department of General and Experimental Pathology, University of Vienna, Austria
^b Department of Organic Chemistry, University of Vienna, Austria
^c Institute of Immunology and Allergology, University of Bern, Switzerland

The major birch pollen allergen Bet v 1 is one of the most extensively characterized allergens both on the molecular and the immunological level. To define conformational B cell epitopes on Bet v 1, we screened filamentous phage libraries expressing circular or linear nonapeptides to select ligands specific for anti-Bet v 1 murine monoclonal antibodies BIP1 and BIP4. The deduced amino acid sequence of the BIP1 ligand was CFPYCYPSESA, and of the BIP4-ligand, CRQTRTMPGC. Both sequences derived from the circular phage library. Alignments to the sequence of Bet v 1 showed no similarities, indicating that the antibodies most likely recognize discontinuous epitopes. Phages displaying these mimotopes were capable of inhibiting interactions of the anti-Bet v 1 monoclonals with Bet v 1 in a dose-dependent manner in ELISA. In contrast, sequence-identical synthetic peptides were ineffective in blocking the antibody–allergen interactions. This is in agreement with the conformational inhomogeneity of the peptides in solution as observed by nuclear magnetic resonance spectroscopy. Intragastric administration of phages expressing the BIP1 mimotope induced a Bet v 1-specific IgG response in Balb/c mice. We conclude that peptide mimotopes, when displayed on phages, may induce a protective IgG response preventing IgE-mediated allergic reactions, suggesting a possible clinical application.—Jensen-Jarolim, E., Leitner, A., Kalchhauser, H., Zürcher, A., Ganglberger, E., Bohle, B., Scheiner, O., Boltz-Nitulescu, G., Breiteneder, H. Peptide mimotopes displayed by phage inhibit antibody binding to Bet v 1, the major birch pollen allergen, and induce specific IgG response in mice. FASEB J. 12, 1635–1642 (1998)

Key Words: Bet v 1 • allergy • phage • mimotope • oral immunization • monoclonal antibodies

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