What are allergens?

Allergens originate from a diverse range of plants, higher animals, and insects. They include proteins and glycoproteins, the majority of which have molecular weights in the range 1-60 kDa. The identification and characterization of inhvidual allergens follows from the use of aqueous extracts of natural source materials for dlagnosis by skin testing, provocation testing, and in vitro methods. Electrophoretic separation techniques, combined with immunoblotting with sera from sensitized patients, yield basic biochemical information and an indication of the number and nature of allergens associated with a particular source material. Cloning from cDNA libraries then opens the door to detailed information on protein structure that is essential for a better understandmg of the mechanisms of sensitization. Allergenic activity is dependent on the ability of proteins to interact with specific IgE antibodies bound to Fc,Ri receptors on mast cells and basophils, and thereby trigger release of inflammatory medators and cytokines that induce and perpetuate the allergic state. The majority of IgE-bindmg epitopes are dependent on the threedimensional structure of the allergens. This has been clearly demonstrated by genetic engineering techniques to produce variant forms of allergens, such as Timothy grass pollen Phl p 5 (I) and birch pollen Bet v 1 (z), which have greatly reduced IgE-binding activity. On the other hand, T-cell epitopes are encoded in specific sequences of amino acids in the primary structure and can be identified by dodecapeptides based on that structure. The cross-reactivity between related allergens can be explained in terms of structural similarities at the epitope level, but, more importantly, this feature provides a basis for designing hypoallergenic variants that hold promise for improved allergen-specific therapeutic vaccination.