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.