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. Author manuscript; available in PMC: 2014 Jan 1.
Published in final edited form as: Biochem J. 2013 Jan 1;449(1):91–99. doi: 10.1042/BJ20121088

Figure 1. Design of a heterotetravalant synthetic allergen as a model system to study mast cell degranulation.

Figure 1

A) Crystal structure of the peanut allergy protein Ara h 3 (PDB 3C3V) with the 4 immunodominant epitopes shown. To mimic the multiple different epitopes present on a natural allergen such as Ara h 3, we synthesized the heterotetravalent synthetic allergen (HtTA) made of two distinct haptens, each with a valency of 2. Bivalent ligands composed of 2 copies of one hapten (HmBA-1, HmBA-2), or composed of 1 copy of each of the two haptens (HtBA) were also synthesized as controls. B) In an allergic reaction, the allergen binds to polyclonal IgE antibodies found on the surface of mast cells. The cross-linking of the IgE receptor, FcεRl, initiates a signaling cascade that results in mast cell degranulation. C) In the HtTA design, multiple different haptens of HtTA simultaneously bind to their respective IgE antibodies, mimicking the involvement of polyclonal antibodies in a natural allergic response. D) When the mast cells have only a single type of IgE on their surface that is specific for only one of the haptens, the HtTA can only bind bivalently to the IgE, which does not provide sufficient cross-linking to stimulate a degranulation response.