5 FcγRIIb shows inhibitory activity across epitopes and allergens in allergen mixtures: abrogating IgE signalling for multiple allergens
A key difference between allergen neutralization and engagement of FcγRIIb is the breadth of activities, not only in terms of affinity but also in terms of specificity. As discussed above, neutralization is only possible for a given epitope on a given allergen. Unexpectedly, engagement of FcγRIIb not only blocks activation of IgE antibodies with a different epitope than the IgG exhibits but is also effective for entirely different allergens as long as the allergen recognized by the IgG antibody is present in the mixture. Specifically, peanut-allergic local and systemic responses against whole peanut allergen extract could be blocked by immunization against a single allergen, specifically Ara h1 or Ara h213,24. Even though mice were allergic to multiple peanut allergens, immunization against a single allergen was sufficient to block allergic responses. Furthermore, polyclonal antibodies against Ara h 1 or Ara h 2, as well as a mAb against Ara h 2 were able to abrogate allergic responses induced by the peanut extract25, confirming earlier data for cat allergy, an allergy which is, however, mostly driven by the single allergen Fel d 126. This protective effect of Ara h 1 and Ara h 2 antibodies was again strictly dependent on the presence of functional FcγRIIb. In absence of the inhibitory receptor, no reduction in allergic symptoms could be observed. Hence, IgG complexes with a single allergen are able to abrogate IgE-signalling induced by complex allergen mixtures.