Allergy development on a clonal level: development of IgE clonotypes with differential allergenicity

• Applicant: Dr. Chinweike Christopher Udoye, Ph.D.
• Subject Area: Immunology ; Clinical Immunology and Allergology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 566390172

Food allergies are hypersensitivity reactions that resemble common, costly, and potentially life-threatening diseases. Antibodies of the IgE subclass have long been known to trigger allergic reactions. However, recent studies suggest that not all IgE antibodies can mediate allergic symptoms and that antibodies of another subclass, called IgG, can inhibit IgE-mediated allergic reactions. Generating anti-allergenic IgG antibodies is one of the principles behind allergy-specific immunotherapies. This therapy can provide tolerance to the allergen, but it is time-consuming, and its efficiency is inconsistent between patients and allergy types. The messenger substance (cytokine) IL-13 was found to be dispensable for IgE production but required for the production of highly allergenic IgE antibodies, although the role of IL-13 in this process is not fully understood. Our preliminary work suggests that only those IgE clones correlate with allergic symptoms. i.e they either bind the allergen with higher affinity than IgG antibodies or bind to distinct epitopes not bound by IgG antibodies (=divergent IgE). Based on these findings, I hypothesize that these "divergent" IgE clones are the main drivers of allergy development and that the cytokine IL-13 is involved in the generation of divergent IgE clones, because this cytokine affects the B cells that produce and secrete IgE and IgG antibodies. The experiments described in this proposal address this hypothesis by deep sequencing of the IgE and IgG1 antibody repertoires, and the generation of divergent and non-divergent IgE, in the presence and absence of IL-13. The study is expected to lead to a better understanding of how allergenic and anti-allergenic antibodies develop. Its findings may help to improve existing allergen-specific immunotherapies.

• DFG Programme: Research Grants