Low-affinity but high-avidity interactions may offer an explanation for IgE-mediated allergen cross-reactivity
| Autor: | Pascal Krenger, Xinyue Chang, Xuelan Liu, Alexandra Wallimann, Mona O. Mohsen, Martin F. Bachmann, M Vogel, Lisha Zha |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Allergy Immunology specificity 610 Medicine & health Cross Reactions medicine.disease_cause Immunoglobulin E Cross-reactivity 03 medical and health sciences 0302 clinical medicine Allergen avidity Fel d 1 medicine Hypersensitivity Immunology and Allergy Animals Humans Avidity allergen cross‐reactivity biology Chemistry Allergens medicine.disease allergy 030104 developmental biology 030228 respiratory system Allergen‐Specific Immunotherapy and Biologics Immunoglobulin G biology.protein Cats Original Article affinity IgE antibody Antibody ORIGINAL ARTICLES Type I hypersensitivity |
| Zdroj: | Allergy Chang, Xinyue; Zha, Lisha; Wallimann, Alexandra; Mohsen, Mona O; Krenger, Pascal; Liu, Xuelan; Vogel, Monique; Bachmann, Martin F (2021). Low-affinity but high-avidity interactions may offer an explanation for IgE-mediated allergen cross-reactivity. Allergy, 76(8), pp. 2565-2574. Wiley 10.1111/all.14864 |
| DOI: | 10.48350/163092 |
| Popis: | Background Allergy is a global disease with overall frequencies of >20%. Symptoms vary from irritating local itching to life‐threatening systemic anaphylaxis. Even though allergies are allergen‐specific, there is a wide range of cross‐reactivities (eg apple and latex) that remain largely unexplained. Given the abilities of low‐affinity IgG antibodies to inhibit mast cells activation, here we elucidate the minimal affinity of IgE antibodies to induce type I hypersensitivity. Methods Three mature (high‐affinity) IgE antibodies recognizing three distinct epitopes on Fel d 1, the major cat allergen, were back‐mutated to germline conformation, resulting in binding to Fel d 1 with low affinity. The ability of these IgE antibodies to activate mast cells in vitro and in vivo was tested. Results We demonstrate that affinities as low as 10−7 M are sufficient to activate mast cells in vitro and drive allergic reactions in vivo. Low‐affinity IgE antibodies are able to do so, since they bind allergens bivalently on the surface of mast cells, leading to high‐avidity interactions. Conclusions These results suggest that the underlying mechanism of allergen cross‐reactivity may be low‐affinity but high‐avidity binding between IgE antibodies and cross‐reactive allergen. Germline IgE antibodies were of low affinity to allergen. Low‐affinity IgE antibodies are able to activate mast cells in vitro and in vivo via high‐avidity binding. Allergen A induces specific high‐affinity IgE antibodies, but with low affinity to allergen B, which could activate mast cells by high‐avidity binding to IgE antibodies. Abbreviations: OD595, optical density 595 nm; PBS, phosphate‐buffered saline. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|