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A molecular model of type I allergy: Identification and characterization of a nonanaphylactic anti-human IgE antibody fragment that blocks the IgE-FcϵRI interaction and reacts with receptor-bound IgE

Authors
Journal
Journal of Allergy and Clinical Immunology
0091-6749
Publisher
Elsevier
Volume
108
Issue
3
Identifiers
DOI: 10.1067/mai.2001.117593
Keywords
  • Allergy
  • Asthma
  • Ige
  • FcϵRi
  • Competitor
  • Therapy
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Background: The IgE-mediated activation of effector cells and antigen-presenting cells through the high-affinity receptor for IgE (FcϵRI) represents a key pathomechanism in type I allergy and many forms of asthma. Objective: We sought to establish an in vitro molecular model for the interaction of human FcϵRI, IgE, and the corresponding allergen and to identify monoclonal anti-human IgE antibodies with a therapeutic profile different from previously established anti-IgE antibodies. Methods: Human FcϵRI α chain, a human monoclonal allergen-specific IgE antibody (chimeric Bip 1), and the corresponding allergen, the major birch pollen allergen Bet v 1, were produced as recombinant proteins and analyzed by means of circular dichroism and native overlays, respectively. Using this molecular model, as well as negative stain immunoelectron microscopic analysis, and in vitro cultivated human basophils, we characterized mouse anti-human IgE antibodies. Results: We established a molecular model for the interaction of human IgE with FcϵRI. Using this molecular model, we identified a nonanaphylactic anti-human IgE antibody fragment (Fab12), which blocked the IgE-FcϵRI interaction and reacted with effector cell–bound IgE. Conclusion: Fab12 represents a candidate molecule for therapy of atopy and asthma because it can be used for the depletion of circulating IgE antibodies, as well as for the depletion of IgE-bearing cells. (J Allergy Clin Immunol 2001;108:409-16.)

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