What establishes a protein as an allergen?

There is little known about the factors that determine the allergenicity of food proteins. Apparently, the ability of a food protein to induce an allergic response requires its presence in substantial amounts in the food supply, its durability during food processing, and its resistance to digestion in the gastrointestinal tract. In addition to the mode and degree of exposure, structural characteristics appear to play an important role for the capacity of a protein to modulate the immune response towards allergic reactions. Until now, however, there has been no indication for common structural characteristics of linear T cell or linear IgE (B cell) epitopes and the knowledge of structural characteristics of conformational IgE binding sites is very limited. Experimental data point only to certain surface areas of allergenic proteins which are important for IgE binding. Therefore, it is not possible to suggest any structural motif or conformational sequence pattern common to all allergenic proteins. Furthermore, glycosylation appears not to be a common critical determinant of allergenicity since food allergens comprise both glycoproteins and nonglycosylated proteins. Based on the few published three-dimensional structures of allergenic proteins including food proteins, one unifying feature of allergens appears to be their spherical shape. The three-dimensional structures of many more allergens have to be determined, however, to allow for a better understanding of the molecular basis of allergenicity. Most recently, new ideas have been introduced as to why certain biochemical or biologic functions such as enzymatic activities may predispose a protein to become an allergen. Proteolytically active allergens have been demonstrated to irritate the human mucosal surface, to enhance their own transmucosal uptake, and to augment IgE production. Therefore, the functional activity of some allergens may play a role among other factors in the process of sensitization and allergic responses.