Allergy research 
at the department of clinical microbiology University of Eastern Finland 
Kuopio, Finland

It is not known what is the property of most of the allergenic proteins which make them allergenic. It is neither known why most individuals do not mount a productive immune response against them resulting in IgE production and the immediate-type of allergy.

There is some information, for example, size, solubility, resistance to digestion, and other quite unspecific characteristics which in fact do not explain the allergenic capacity of these proteins, that is, their capacity to induce the T-helper type 2 (Th2) differentiation of CD4+ T lymphocytes. Th2 cells play a pivotal role in the immediate type of allergy, such as pollen-induced rhinitis or animal dust-induced asthma, by secreting interleukin-4 which stimulates IgE production.

Lately, factors not directly related to allergenic proteins have aroused interest in that they could account for allergenicity. These include various innate immunity-related elements, such as Toll-like receptors and their ligands. Despite the interest they have raised, they do not tell, for example, why one of the most prevalent allergens, birch pollen Bet v 1, is allergenic. Most probably, immunogenicity alone is not the thing. Most probably, adjuvant-like capacity associated with pollen is not the thing. If adjuvant-like capacity were decisive, all immunogenic proteins in pollen should be allergens, as well as all the other proteins encountered by the human immune system in association with pollen. Enzyme activity, suggested as a characteristic of allergens,  is a property of only a minority of allergenic proteins.

It has been realized in recent years that the naive T-cell (or T-cell receptor, TCR) repertoire is of pivotal importance for the diversity, quality and magnitude of a primary T-cell response. Therefore, the way T-helper cells recognize antigen (or allergen) by their TCRs may be a factor shifting the delicate balance between recognition and ignorance or between  Th2 (allergenic) and T-helper type 1 (nonallergenic) responses in favor of allergic or healthy outcome. Our hypothesis is that for a protein to be potentially an allergen, its recognition by the adaptive immune system in a certain TCR avidity window is necessary: If TCR avidity is too low for recognition, the protein is ignored; if TCR avidity is strong for recognition, the T-helper type 1 response is favored; if TCR avidity is in between, allergic sensitization (Th2 deviation) is possible.

Allergy and Allergens are mysterious