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

Sylvia Laffer, Erik Hogbom, Kenneth H. Roux, Wolfgang R. Sperr, Peter Valent, Hans C. Bankl, Luca Vangelista, Franz Kricek, Dietrich Kraft, Hans Grönlund, Rudolf Valenta

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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 anti-bodies 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.

Original languageEnglish
Pages (from-to)409-416
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume108
Issue number3
DOIs
Publication statusPublished - Sep 2001

Keywords

  • Allergy
  • Asthma
  • Competitor
  • FcεRI
  • IgE
  • Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this