3 High affinity antibodies are required for
allergen-neutralization
The most straight-forward 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 monovalencys, in contrast to avidity that
only plays a minor role. Indeed, low affinity IgG antibodies failed to
neutralize allergens and did not block basophil/mast cell activation
both in vitro as well as in vivo 21. 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.