背景：臨床和實驗分析表明，過敏原IgE抗體表位-副表位的相互交聯(lián)是導致效應細胞活化和lgE介導的食物過敏的主要初始步驟。本研究的目的是初步研究和評估阿糖胞苷H2特異性IgE表位樣肽，它可以結合過敏原特異性IgE副表位和抑制效應細胞活化。
方法：該研究進行了肽的生物篩選、IgE結合、選擇和定位。生產了用于所有功能實驗的合成肽。對LAD2人肥大細胞系進行 ImmunoCAP抑制、嗜堿性粒細胞和肥大細胞活化試驗。
結果：我們鑒定并篩選了三種線性肽（DHPRFnRDDVA、DHPRYGP和DHPRFST），免疫印跡分析顯示它們能與花生過敏個體的lgE抗體結合。這些肽序列與與Ara h 2的螺旋2和螺旋3之間的環(huán)狀結構序列相比對，構象圖顯示這些肽與Ara h 2的螺旋2和螺旋6的表面相匹配，而與其他花生過敏原不匹配。在ImmunoCAP抑制實驗中，這些多肽顯著抑制IgE與Ara h 2的結合（p< 0.001）。在嗜堿性粒細胞和肥大細胞活化實驗中，這些多肽能顯著抑制Ara h 2誘導的效應細胞活化（p< 0.05），增加了Ara h 2半數(shù)最大有效濃度（p< 0.05）。這些肽鏈與特異性IgE的結合不會引起嗜堿性粒細胞或肥大細胞的活化。
結論：這些研究表明，上述肽鏈可降低Ara h 2的致敏活性并抑制依賴lgE的嗜堿性粒細胞和肥大細胞的激活。這些觀察結果可為基于表位-副表位阻斷的食物過敏治療提供一種新的治療策略。


原始出處
Clin Exp Allergy
Title：Arah2-specific IgE epitope-like peptides inhibit the binding of IgE to Arah2 and suppress lgE-dependent effector cell activation
DOI: 10.1111/cea.14314
Abstract:
Background: Clinical and experimental analyses indicate a pathognomonic role for allergen IgE crosslinking through epitope–paratope interactions as a major initial step in the cascade leading to effector cell activation and clinical manifestations of lgE-mediated food allergies. We aimed to undertake the initial development and assessment of Ara h 2-specific IgE epitope-like peptides that can bind to allergen specific IgE paratopes and suppress effector cell activation.
Methods: We performed biopanning, screening, IgE binding, selection and mapping of peptides. We generated synthetic peptides for use in all functional experiments. ImmunoCAP inhibition, basophil and mast cell activation tests, with LAD2 cells, a human mast cell line were performed. Twenty-six children or young adults who had peanut allergy were studied.
Results: We identified and selected three linear peptides (DHPRFNRDNDVA, DHPRYGP and DHPRFST), and immunoblot analyses revealed binding to lgE from peanut-allergic individuals. The peptide sequences were aligned to the disordered region corresponding to the loop between helices 2 and 3 of Ara h 2, and conformational mapping showed that the peptides match the surface of Ara h 2 and h 6 but not other peanut allergens. In ImmunoCAP inhibition experiments, the peptides significantly inhibit the binding of IgE to Ara h 2 (p< 0.001). In basophil and mast cell activation tests, the peptides significantly suppressed Ara h 2-induced effector cell activation (p<0 .05) and increased the half-maximal Ara h 2 effective concentration (p<0 .05). Binding of the peptides to specific IgEs did not induce activation of basophils or mast cells.
Conclusions: These studies show that the indicated peptides reduce the allergenic activity of Ara h 2 and suppress lgE-dependent basophil and mast cell activation. These observations may suggest a novel therapeutic strategy for food allergy based on epitope–paratop blocking.
First Author: Peter Koro?ec 
Corresponding author: Peter Koro?ec 
Correspondence: Peter Koro?ec, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik 36, 4204 Golnik, Slovenia.
Email: peter.korosec@klinika-golnik.si