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
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Allergy_-_2021_-_Chang_-_Low_affinity_but_high_avidity_interactions_may_offer_an_explanation_for_IgE_mediated_allergen.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC). Download (1MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Chang, Xinyue, Liu, Xuelan, Bachmann, Martin (B) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1398-9995 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Lee-Anne Brand |
Date Deposited: |
20 Jan 2022 07:31 |
Last Modified: |
29 Mar 2023 23:38 |
Publisher DOI: |
10.1111/all.14864 |
PubMed ID: |
33866583 |
Uncontrolled Keywords: |
IgE antibody affinity allergen cross-reactivity allergy avidity specificity |
BORIS DOI: |
10.48350/163092 |
URI: |
https://boris.unibe.ch/id/eprint/163092 |
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