Birch blossoms release their pollen with the molecule Bet v 1 (turquoise). Bet v 1 loaded with an iron-containing ligand (yellow with gray ball) does not act as an allergen. (Source: University of Veterinary Medicine, Vienna/, lochstampfer, Luis F. Pacios)While it is known that a specific birch pollen protein causes the immune system to overreact, the exact reason why many people are allergic to birch pollen has not yet been fully clarified. Now, scientists at the Vetmeduni Vienna have discovered what makes it an allergen. The pollen protein can bind iron. Without iron load the protein becomes an allergen. Environmental factors are possibly the reason for low iron loads in plants. This could explain the increasing numbers of allergies. The research data were published in the Journal of Biological Chemistry.   
Allergies in humans and animals are on the increase. An allergic reaction can cause unpleasant symptoms, such as hay fever, food intolerance or skin rashes. They can also cause acute and life-threatening symptoms, such as asthma or anaphylactic shock. 
A single pollen protein is responsible for allergies 
One of the most well-known allergens, substances that cause allergies, is the so-called “Bet v1,” which comes from birch pollen (Betula verrucosa). The protein was first produced artificially in a Vienna laboratory 25 years ago, and is now being used as an allergen model for research throughout the world. Bet v 1 is the principal allergen among hundreds of other proteins in birch pollen. It renders the immune system hypersensitive and leads to the formation of disease-causing antibodies, known as IgE immunoglobulins, in 95 percent of people with a pollen allergy. 
Birch pollen protein in its iron-loaded state is not allergenic 
Until recently, it was not known why harmless molecules trigger allergies at all. Scientist Franziska Roth-Walter and her colleagues from the Messerli Research Institute found the possible cause. Bet v 1 is very similar to the human protein Lipocalin 2 in terms of structure. Lipocalin 2, mainly present in the lung, and Bet v 1 possess so-called molecular pockets with which they can bind iron. When these pockets remain empty, the birch pollen protein becomes an allergen and is able to cause allergic reactions in humans and animals. The protein manipulates so-called T-helper 2 cells (Th2 cells), a certain type of immune cells, toward allergy. The human protein Lipocalin 2 also performs tasks of the immune system, depending on its iron loading. 
Origin of allergy investigated in the model of birch pollen 
In people and animals with allergies, Th2 cells are predominant compared to Th1 cells. Th2 cells play an important role in allergic reactions and in combating parasites. Th1 cells serve to defend the body against bacterial and viral infections.
"A typical feature of allergies is the disruption of the balance between the Th1 and Th2 immune response," said Professor Erika Jensen-Jarolim, head of the Department of Comparative Medicine at the Messerli Research Institute. "Investigations currently in progress indicate that we can directly transfer the principle of birch pollen allergens to other allergens with a similar molecular structure. We are thus starting to understand- for the first time- why allergies to pollen, foodstuffs and fungal spores actually arise in the first place." 
Environmental factors determine the iron loading of the pollen protein 
Scientists at the Messerli Research Institute, a combined facility of the Vetmeduni Vienna, the Meduni Vienna an der University of Vienna, are currently investigating the mechanisms that may contribute to reduced iron loading of Bet v 1 in plants.
"Iron loading of the birch protein may be connected to the aggravated environmental conditions acting on plants," said Jensen-Jarolim. "In fact, there may be a direct connection between environmental pollution and rising allergy statistics. The most important conclusion from our work is that, in the future, it would make sense to specifically load allergenic molecules of the Bet v 1 type with iron when they are used as allergy-specific immunotherapy in allergic patients. By doing so, this treatment- which currently takes two to four years- can be greatly shortened and its efficiency can thus be enhanced."