Low-affinity but high-avidity interactions may offer an explanation for IgE-mediated allergen cross-reactivity.
Allergy
; 76(8): 2565-2574, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33866583
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Alérgenos
/
Hipersensibilidade
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article