Allergy modulation by cytokine-mimetic peptides and particle

The allergy epidemic seen in recent years has led to more than 150 million people in Europe and about one billion worldwide to suffer from chronic allergic diseases, such as allergic rhinitis, asthma and atopic eczema. Allergies result from an overwhelming immune response to allergen sources that are harmless to most people in the population. Pollen is one of the most important sources of airborne allergens, causing allergies in approximately 40% of patients suffering from respiratory allergies. Although humans are all exposed to a variety of allergen sources, only some individuals will develop allergies and only some compounds in a source act as allergens. Despite intensive studies, it still remains unclear why only certain compounds are allergens and why they are differentially recognized by the immune system of predisposed and non-predisposed individuals. A recent study found that water-soluble pollen allergens lack the ability to induce specific T regulatory cells, which are known to actively suppress allergic responses. In addition, their high solubility in water seems to be a critical determinant for induction of allergy because molecules that remained associated to the pollen particle induced robust regulatory/anti-allergic responses. Based on these findings, we propose that both the form (soluble x particulate) and the context (immune modulatory signals) are fundamental in determining why only some compounds are allergens. We postulate that the allergenic activity of molecules can be altered or modulated by stably coupling them to particles in combination with immune modulatory molecules capable of inducing T regulatory cells. We will specifically investigate the immune responses induced by soluble and particle-conjugated preparations of the major birch pollen allergen Bet v 1 in combination with cytokine mimetic peptides shown to have anti-inflammatory activity and to induce regulatory cells. We foresee that the knowledge gained in this project will uncover new perspectives for the prevention and treatment of allergic diseases.