Human IgE against the major allergen Bet v 1--defining an epitope with limited cross-reactivity between different PR-10 family proteins.
Bottom Line: The interaction between IgE and allergen is a key event at the initiation of an allergic response, and its characteristics have substantial effects on the clinical manifestation.We here display the usefulness of allergen-specific human monoclonal IgE as a tool in studies of the crucial molecular interaction taking place at the initiation of an allergic response.Such studies may aid us in development of better diagnostic tools and guide us in the development of new therapeutic compounds.
Affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.Show MeSH
Mentions: Different Bet v 1-isoforms have shown varying ability to initiate allergic responses 15,16 and not all IgE-binding epitopes may be shared between the different isoforms, a fact that potentially could complicate diagnosis and specific immunotherapy. We therefore profiled the cross-reactivity between our human Bet v 1-specific IgE-derived scFv and three naturally existing Bet v 1-isoforms (Fig.3). All four scFv, including M0418 that was selected on Bet v 1.0102, did bind the major isoform Bet v 1.0101. It was thus not possible to select binders from this combinatorial IgE library without cross-reactivity to Bet v 1.0101, indicating that epitopes carried on this isoform were major contributors in the sensitization of the allergic donors to Bet v 1-like allergens. Notably, all four scFv showed high reactivity with Bet v 1.0102, an isoform suggested to be a naturally occurring hypoallergen (i.e. a naturally existing Bet v 1-isoform with reduced allergenicity) 15,16,39. In contrast, only two of the available Bet v 1-specific scFv, B10 and B13, showed binding to Bet v 1.0112, another naturally existing variant only differing from Bet v 1.0101 by a single amino acid substitution (F62L). Bet v 1.0112 has also been the foundation for design of two hypoallergenic variants, Bet v 1.2595 and Bet v 1.2744 22, carrying 4 and 9 mutations, respectively, to which none of our four scFv showed any detectable binding, supporting their hypoallergenic properties.
Affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.