An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor Fc?RIIb - 06/11/18
Abstract |
Background |
Induction of allergen-specific IgG antibodies is a critical parameter for successful allergen-specific immunotherapy. IgG antibodies can inhibit IgE-mediated mast cell activation through direct allergen neutralization or through the inhibitory receptor FcγRIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation.
Objective |
Here we addressed the question of affinity thresholds of allergen-specific IgG antibodies for inhibition of mast cell activation using 2 different mAbs against the major cat allergen Fel d 1 both in vitro and in vivo in mice.
Methods |
Sequences of the 2 high-affinity mAbs were back-mutated to germline, resulting in low-affinity (10−7 mol/L) antibodies of the exact same specificity.
Results |
Using these newly generated recombinant antibodies, we demonstrate that low-affinity antibodies are still able to inhibit mast cell activation through FcγRIIb but do not neutralize the allergen.
Conclusion |
Antibody affinity dictates the mechanism of mast cell inhibition, and IgG antibodies triggering the inhibitory FcγRIIb pathway can show a broader cross-reactivity pattern than previously thought. This indicates that allergen-specific immunotherapy generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Allergy, vaccination, FcγRIIb-mediated inhibition, Fel d 1, low-affinity antibodies
Abbreviations used : BMMC, DARPin, FACS, RU, SIT
Plan
Supported by funding of the Swiss National Science foundation (SNF grant 31003A 149925 to M.F.B.). |
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Disclosure of potential conflict of interest: M. Cragg has consultant arrangements with Bioinvent International and has received payment for lectures from Baxalta. M. F. Bachmann is a board member of Hypo Pet. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 5
P. 1529 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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