P01 (2026 - 2030) Allergenicity of IgE and IgG1 clonotypes in murine food allergy

Rudolf Manz (UzL), Anke Fähnrich (UzL), Christopher Chinweike Udoye (UzL)

Project Summary 

Allergen-specific IgE plays a central role in the pathogenesis of food allergy, but its titer correlates poorly with the development of allergy. This may be because the allergic Th2 immune response generates antibodies with distinct pro- and anti-allergenic properties. High-affinity IgE is required to induce potent mast cell activation that ultimately leads to allergic anaphylaxis, whereas low-affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgG antibodies can inhibit IgE-mediated mast cell activation, thereby protecting IgE-positive individuals from the development of allergy. Allergen neutralization is an important mechanism of IgG-mediated allergy prevention, i.e., IgG competes with IgE for binding to allergenic proteins. Since most IgE is formed by sequential class switching from IgG1 precursors, allergen-specific IgG1 and IgE share similar antigen binding sites that are optimally suited for allergen neutralization. The mechanisms that determine the allergenicity of IgE antibodies are not fully understood. This project will define the impact of individual antibody clonotypes and their allergenic and antiallergenic properties for the development of food allergy and related type 1 allergies.