Epitope recognition patterns in grass pollen allergy

Respiratory allergies elicited by pollen, fungal spores, house dust mites or dander from pets affect the quality of file of a large proportion of the population. Symptoms range from mild hayfever to severe bronchial asthma. The only causative therapy is allergen immunotherapy (AIT), in which increasing amounts of an extract from the respective allergen source is either injected (subcutaneous AIT) or given under the tongue as a tablet (sublingual AIT) over the course of several years. However, the long duration of the therapy required for sustained improvement of the symptoms as well as the sometimes observed allergic side effects leads to premature termination of the therapy by many patients. During AIT, the repeated contact with the allergens stimulates the immune system to produce allergen-specific antibodies of the IgG class that compete with the allergy- inducing IgE antibodies for binding to the allergens, thereby preventing the onset of an allergic reaction. It has been observed that high concentrations of protective allergen-specific IgG antibodies are formed already in the first year of therapy. Nevertheless, a sustained reduction of allergic symptoms lasting beyond the end of the therapy is achieved only if the therapy is continued for at least three years. The reason for this discrepancy is still unknown. In this project, we will examine the development of antibody response during AIT in patients allergic to grass pollen, which is among the most prevalent elicitors of respiratory allergy. The hypothesis underlying this project is that the exact composition of allergen-specific antibodies, particularly with respect to their binding sites on the allergenic proteins, determines their biological impact. Therefore, we will obtains serum samples from grass pollen-allergic patients before and one year after start of AIT and measure the concentrations of allergen-specific antibodies as well as the location of their binding sites on the surface of the allergens. To this end, we will produce a panel of artificial chimeric proteins, each of which displaying only a part of the molecular surface of each of the most important grass pollen allergens. With these tools, we will be able to tackle several questions: Does the repertoire of allergy-inducing IgE antibodies change during the first year of therapy? Do the newly formed protective IgG antibodies recognize the same patches on the allergen surface as the IgE antibodies? Is there a difference between subcutaneous and sublingual AIT? With these data, we hope to provide new insights into the immunological changes contributing to disease modification by AIT. The long-term goal of this research is the development of novel therapy concepts with benefits such as fewer side effects and shorter duration of treatment.