3 High affinity antibodies are required for
allergen-neutralization
The most straightforward way for IgG antibodies to inhibit activation of
basophils and mast cells by allergens is direct neutralization of the
allergen in competition with allergen-specific
IgE10,20.
This mechanism, now, corresponds to the above discussed and by
physico-chemists’ preferred interaction of antibodies with ligands; it
happens in solution, or at least within tissue fluids and antibodies
typically bind with one arm only. Hence, because this epitope-specific
interaction is a competitive one, it is largely promoted by high
affinity and monovalency, in contrast to avidity which only plays a
minor role in direct neutralization. Indeed, low affinity IgG antibodies
failed to neutralize allergens and did not block basophil/mast cell
activation both in vitro as well as in vivo21. As a further
restriction, neutralizing antibodies must recognize the same allergen as
the IgE and preferably even the same epitope. This contrasts with
interaction mediated via FcγRIIb, as described below. Indeed, low
affinity IgG antibodies fail to neutralize the allergen but may
efficiently block cellular activation by engaging FcγRIIb.