What Makes a Food Protein an Allergen? (1)

The most common food allergies known to affect children are IgE-mediated reactions to cow’s milk, eggs, peanuts, soybeans, wheat, fish, and tree nuts. Although most childhood food allergies are outgrown, allergies to peanuts, tree nuts, and fish are rarely resolved in adulthood. In adults, the most common food allergies are to peanuts, tree nuts, fish, and shellfish. Food allergens can be classified into two groups, broadly based on their ability to only elicit clinical symptoms in previously sensitized individuals (incomplete food allergens) or their ability to sensitize and elicit reactions in susceptible individuals (complete food allergens). Incomplete food allergens comprise those proteins that can only elicit clinical symptoms due to their homology with another allergen. Complete food allergens comprise those proteins that can both sensitize and elicit clinical symptoms.

A review of the major allergens in the commonly allergenic foods seems to confirm the importance of this characteristic in making a food protein an allergen. The major allergens of most of the commonly allergenic foods, includ- ing milk, eggs, peanuts, soy, tree nuts, and wheat, represent major protein constituents (>1%) of their respective foods.

The requirement that IgE be cross-linked on effector cells to release the mediators of allergic symptoms dictates that there be at least two high-affinity, IgE-binding epitopes on a single allergen. Two categories of IgE-binding epitopes, linear and conformational, are generally considered to occur in food allergens. Linear epitopes are important to food allergens mainly because the immune system encounters them only after they have been partially denatured and digested by the human gastrointestinal (GI) tract. IgE-binding epitopes were identified throughout the length of the Ara h 1 molecule. Ten IgE-binding epitopes were identified in Ara h 2 and four in Ara h 3 using the same methods. Linear, IgE-binding epitopes have been mapped for other major food allergens, including those in milk, soy, shrimp, and cashew.

Resistance to denaturation and digestion is thought to be an important characteristic of food allergens because the longer a significant portion of the protein remains intact, the more likely it is to encounter cells of the immune system. When stability of the major allergens from these foods is disrupted by reduction of disulfide bonds, the allergens were strikingly sensitive to pepsin digestion and lost their allergenicity. Ara h 2 structures are not completely randomized when the disulfide bonds are reduced but instead are predominated by a β-pleated sheet and β- turn configuration. The Ara h 2 molecule is a very ordered protein, even if its disulfide bonds are not intact. Only the reduced form of Ara h 2 becomes susceptible to rapid digestion with pepsin, chymotrypsin, or trypsin, indicating a reduction in its over- all allergenicity. The structure of peanut allergen, Ara h 1, might also con- tribute to its stability. Ara h 1 tertiary structure consists of two sets of opposing anti-parallel β-sheets in Swiss roll topology joined by an interdomain linker. The formation of a homotrimer might also afford the molecule protection from protease digestion and denaturation.

1. G. A. Bannon, What makes a food protein an allergen? Curr. Allergy Asthma Rep. 4, 43–46 (2004).