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 h2 13,24. Even though mice were allergic
against multiple peanut allergens, immunization against a single
allergen was sufficient to block allergic responses. Furthermore,
polyclonal antibodies against Ara h 1 or Ara h2, as well as a mAb
against Ara h 2 were able to abrogate allergic responses induced the
peanut extract 25, confirming earlier data for allergy
against Fel d 1 , an allergy which is, however, mostly driven by a
single allergen 26. 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.