International Immunology Center, Anhui Agricultural University, Anhui, China.
Immunology, RIA, Inselspital, University of Bern, Bern, Switzerland.
Allergy. 2021 Aug;76(8):2565-2574. doi: 10.1111/all.14864. Epub 2021 May 28.
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.
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.
We demonstrate that affinities as low as 10 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.
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.
过敏是一种全球性疾病，总体发生率超过 20%。症状从局部瘙痒到危及生命的全身性过敏反应不等。尽管过敏是过敏原特异性的，但仍有很大一部分交叉反应（例如苹果和乳胶）尚未得到充分解释。鉴于低亲和力 IgG 抗体能够抑制肥大细胞的激活，我们在此阐明 IgE 抗体引起 I 型超敏反应的最小亲和力。
将识别主要猫过敏原 Fel d 1 上三个不同表位的三个成熟（高亲和力）IgE 抗体反向突变为种系构象，导致与 Fel d 1 的结合亲和力降低。测试了这些 IgE 抗体在体外和体内激活肥大细胞的能力。
我们证明，亲和力低至 10 -10 M 就足以在体外激活肥大细胞并在体内引发过敏反应。低亲和力 IgE 抗体能够做到这一点，因为它们在肥大细胞表面以二价结合过敏原，导致高亲和力相互作用。
这些结果表明，过敏原交叉反应的潜在机制可能是 IgE 抗体与交叉反应性过敏原之间的低亲和力但高亲和力结合。
