Immunity to Bet v 1 in allergic and non-allergic subjects

Allergic diseases are a major global public health problem and their prevalence has been increasing continuously affecting almost 30% of the world population. Allergy is a chronic condition involving a misguided reaction of the immune system to harmless foreign substances called allergens. In people prone to allergies the immune system produces a special kind of antibodies, the so called IgE antibodies, against allergens. Complexes of allergens and IgE antibodies activate mast cells, and as a result, these cells release substances, among them histamine, which cause allergic symptoms such as rhinitis, conjunctivitis, asthma, skin manifestations and in the worst case anaphylaxis. Currently, allergen-specific immunotherapy is the only treatment for allergic diseases and the success of immunotherapy is associated with the production of IgG antibodies directed against the allergens, which block the binding of IgE antibodies to allergens. Birch pollen is a dominant airborne allergen source in countries of the Northern Hemisphere, Middle and Northern Europe and Russia. Birch pollen allergy affects more than 100 million patients worldwide and is predominantly mediated by the major birch pollen allergen, Bet v 1. Owing to the fact that proteins with a similar structure as Bet v 1 also exists in different plant food allergen sources (e.g., apple, peach, kiwi, celery, carrot, soy, hazelnut, peanut, pear, cherry), the majority of birch allergic patients is also allergic to different foods. In this project, a detailed analysis of the IgE and IgG antibody responses in subjects with birch pollen allergy and in non-allergic subjects will be performed using a high resolution micro-arrayed allergen assay. This assay will include the major birch pollen allergen Bet v 1, the most common Bet v 1-related food allergens and Bet v 1-peptides. In addition, this project will also investigate the responses of T cells (i.e., immune cells that play a role in the adaptive immune response and immune tolerance) in subjects with and without allergy to Bet v 1. The project will therefore provide important knowledge on the normal immune response to Bet v 1, which may be used to develop vaccination and tolerance induction strategies for birch pollen allergy.

More than 30% of the population suffer from allergy. They suffer from respiratory symptoms such as rhinitis and asthma, skin inflammation, food allergy and life-threatening anaphylaxis. The symptoms of allergy are mediated by IgE antibodies which are specific allergens present in different allergen sources. Birch pollen allergy affects more than 200 million people world-wide and is caused by IgE recognition of the major birch pollen allergen Bet v 1. In this project we studied if disease-causing IgE antibodies and normal, harmless IgG antibodies of allergic recognize the same places (i.e., epitopes) on the Bet v 1 allergen. Obtained results showed that IgE and natural IgG antibodies bind to different epitopes which explains why the natural IgG response does not protect birch pollen allergic patients. This can be explained by the fact, that the production of allergen-specific IgE and IgG is derived from different clonal lineages of B cells. We further show that allergen-specific immunotherapy (AIT), a vaccination against the disease-causing allergens, can induce IgG antibodies against the IgE epitopes and thus protect allergic patients. The underlying mechanism is the induction of a de novo immune responses originating from "new" B cells producing protective antibodies. The results of our project are important because they clarify a major controversially discussed scientific question, namely if disease-causing IgE antibodies origin from the same B cells producing IgG, in fact this is not the case, they demonstrate that natural IgG cannot protect allergic patients and that protective IgG can be induced by AIT which is a powerful, inexpensive form of treatment redirecting the patients immune response.