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.