Release date:2018-12-24
JACI:
[IF:13.1]
Immunologic characterization of monoclonal antibodies that modulate human IgE binding to the major birch pollen allergen Bet v 1
https://doi.org/10.1016/S0091-6749(97)70056-3
Abstract:
Background
Background: Bet v 1 and homologous proteins represent major allergens for almost 95% of patients allergic to tree pollen and approximately 70% of those allergic to fruits and vegetables. As yet, no continuous (sequential) IgE epitopes have been determined for Bet v 1, and evidence has accumulated that Bet v 1 IgE epitopes belong to the conformational (discontinuous) type. Objective: A panel of 85 mouse monoclonal anti-Bet v 1 antibodies was raised as a tool with which to study the interaction of human IgE antibodies with Bet v 1. Methods: The epitopes of selected monoclonal antibodies (mAbs) were characterized by mapping with synthetic overlapping peptides and by cross-competition experiments. Cross-reactivity of Bet v 1–specific mAbs with tree and plant food allergens was investigated by Western blotting. The influence of Bet v 1–specific mAbs on the IgE–Bet v 1 interaction was studied by competition assays with immobilized purified recombinant Bet v 1 and by basophil histamine release experiments. Results: Antibodies that increased the IgE binding to Bet v 1 up to fivefold could be defined, whereas others inhibited IgE binding to Bet v 1 up to 99% and competed with the Bet v 1–induced histamine release from patients' basophils. Conclusion: The activity of the enhancing antibodies is interpreted as a stabilization of Bet v 1 states/IgE epitopes, which are either more accessible for certain IgE antibodies or are recognized with higher affinity. Those mAbs that competed with the Bet v 1–IgE interaction, if humanized or produced as recombinant antibody fragments, might be considered as potential tools for local allergy therapy. (J Allergy Clin Immunol 1997;99:374-84.)
All Author:
Serge Lebecque, MDa, Christiane Dolecek, MDb, Sylvia Lafferb, Vincenzo Visco, PhDa, Stéphanie Denépouxa, Jean-Jacques Pina, Christiane Gureta, George Boltz-Nitulescu, PhDb, Anne Weyer, PhDc, Rudolf Valenta, MDb
2018-12-21 Article