Allergen specific antibody therapies

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Antibody therapies are currently the most specific immunological approaches to eliminate or manipulate immune cells because of their high specificity and affinity. The potential of therapeutic antibodies is thereby determined by the interaction of their Ig isotype specific Fc part with specific inhibitory and activating Fc receptors on immune cells. By using an ovalbumin (OVA) induced asthma mouse model we here want to establish allergen specific antibody therapies i) to inhibit allergen dependent IgE activity and IgE production during acute allergic reactions or ii) to induce long term tolerance before or between allergic reactions by targeting dendritic cells. We want to block acute allergic reactions by inducing a negative signal in allergen specific B cells and in IgE target cells like mast cells, basophils and eosinophils via crosslinking the IgG inhibitory receptor FcgammaRIIB with synthezised allergen specific or allergen coupled IgG antibodies (IgG1, IgG2a and IgG2b) and via additionally blocking activating IgG Fcgamma receptors. Additionally, we will analyze an inhibitory potential of synthesized allergen specific and allergen coupled IgM antibodies. These investigations will demonstrate, which Ig Fc part has the highest inhibitory potential in allergic reactions. We further want to analyze the potential of these synthesized antibodies to generate long term tolerance by targeting the allergen to dendritic cells to induce regulatory T cells. In another approach we want to induce long term tolerance by specifically targeting the allergen to different subsets of dendritic cells with allergen coupled DEC-205 or 33D1 antibodies, which recognize a target protein on the surface of CD8+ or CD8- dendritic cells, respectively. In the future, the developed results will be transferred to natural allergens and to the human system.