Food allergy has become a major public health concern in westernized countries, and
allergic reactions to peanuts are particularly common and severe.
Allergens are defined as
antigens that elicit an
IgE response, and most allergenic materials (e.g., pollens, danders, and foods) contain multiple allergenic
proteins. This has led to the concept that there are "major"
allergens and
allergens of less importance. "Major
allergens" have been defined as
allergens that bind a large amount of
IgE from the majority of patients and have
biologic activity. However, the ability of an
allergen to cross-link complexes of
IgE and its high-affinity receptor FcεRI (
IgE/FcεRI), which we have termed its allergic effector activity, does not correlate well with assays of
IgE binding. To identify the
proteins that are the most active
allergens in peanuts, we and others have employed in vitro model assays of
allergen-mediated cross-linking of
IgE/FcεRI complexes and have demonstrated that the most potent
allergens are not necessarily those that bind the most
IgE. The importance of a specific
allergen can be determined by measuring the allergic effector activity of that
allergen following purification under non-denaturing conditions and by specifically removing the
allergen from a complex allergenic extract either by chromatography or by specific immunodepletion. In our studies of peanut
allergens, our laboratory has found that two related
allergens,
Ara h 2 and
Ara h 6, together account for the majority of the effector activity in a crude peanut extract. Furthermore, murine studies demonstrated that
Ara h 2 and
Ara h 6 are not only the major elicitors of
anaphylaxis in this system, but also can effectively desensitize peanut-allergic mice. As a result of these observations, we propose that the definition of a major
allergen should be based on the potency of that
allergen in assays of allergic effector activity and demonstration that removal of that
allergen from an extract results in loss of potency. Using these criteria,
Ara h 2 and
Ara h 6 are the major peanut
allergens.