On the role of allergen-specific IgG subclasses for blocking human
Background: Successful treatment of IgE mediated allergies by
allergen-specific immunotherapy (AIT) usually correlates with the
induction of allergen-specific IgG4. However, it is not clear whether
IgG4 prevents the allergic reaction more efficiently than other IgG
subclasses. Here we aimed to compare allergen-specific monoclonal IgG1
and IgG4 antibodies in their capacity to inhibit type I allergic
reactions by engaging FcγRIIb. Methods: Three monoclonal
antibodies (F127, A044 and G078) against Fel d 1, the major cat allergen
in humans, recognizing three non-overlapping epitopes of Fel d 1 were
tested for their capacity to block human basophils activation in vitro.
The affinity of the three monoclonal antibodies in IgG1 and IgG4 formats
to FcgRIIb were investigated by Biolayer Interferometry.
Results: We found that IgG1, which is the dominant subclass
induced by viruses, binds with a similar affinity to the FcγRIIb as IgG4
and is comparable at blocking human basophil activation from allergic
patients; both by neutralizing the allergen as well as engaging the
inhibitory receptor FcγRIIb. Conclusion: Hence, the IgG
subclass plays a limited role for the protective efficacy of AIT even if
IgG4 is considered the best correlate of protection because it is the
dominant subclass induced by classical AITs.