Browsing by Author "Kaplan, Mark H"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Inhibition of weak-affinity epitope-IgE interactions prevents mast cell degranulation
    (Nature Publishing Group, 2013-12) Handlogten, Michael W; Kiziltepe, Tanyel; Serezani, Ana P; Kaplan, Mark H; Bilgicer, Basar; Department of Pediatrics, IU School of Medicine
    Development of specific inhibitors of allergy has had limited success, in part, owing to a lack of experimental models that reflect the complexity of allergen-IgE interactions. We designed a heterotetravalent allergen (HtTA) system, which reflects epitope heterogeneity, polyclonal response and number of immunodominant epitopes observed in natural allergens, thereby providing a physiologically relevant experimental model to study mast cell degranulation. The HtTA design revealed the importance of weak-affinity epitopes in allergy, particularly when presented with high-affinity epitopes. The effect of selective inhibition of weak-affinity epitope-IgE interactions was investigated with heterobivalent inhibitors (HBIs) designed to simultaneously target the antigen- and nucleotide-binding sites on the IgE Fab. HBI demonstrated enhanced avidity for the target IgE and was a potent inhibitor of degranulation in vitro and in vivo. These results demonstrate that partial inhibition of allergen-IgE interactions was sufficient to prevent mast cell degranulation, thus establishing the therapeutic potential of the HBI design.