P04 (2026 - 2030) Generation of IgE and IgG antibodies with differential allergenic/anti-allergenic potential

Matthias Peipp (CAU), Ralf Ludwig (UzL)

Project Summary 

IgE binds to its high affinity receptor FcεRI to provide effector cells with an antigen/allergen specific receptor to induce the release of mediators such as histamine upon allergen challenge. IgE immune complexes also bind to FcεRII (CD23) where it helps to regulate IgE production and to mediate "IgE-facilitated allergen presentation", important to increase the allergen-specific T cell response by B cells. The action of IgE is partly inhibited  by antibodies with similar specificity of other subclasses, it also depends on its affinity and glycosylation pattern. However, due to the complexity of its actions, the mechanism by which IgE contributes to type 2 immunity, is only partially understood. There is increasing evidence that the nature of individual IgE antibodies (high/low affinity, repertoire, glycosylation), strongly impacts its pathogenic or protective potential. This project will generate well characterized, allergen specific, monoclonal antibodies. It will provide a variety of allergen-specific monoclonal antibody variants with identical VDJ-regions, but distinct hypermutations, affinity, glycosylation pattern and constant regions (IgE or IgG subclass, later also IgA), which can serve as a tool box to unravel basic principles of how these properties control the activation of effector cells, antigen-internalization and presentation, relevant for the role of B cell responses at barrier organs. The expected results also hold the potential to identify novel therapeutic strategies for the treatment of allergic disorders.