IgE and allergen-specific immunotherapy-induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen
IgE and allergen-specific immunotherapy-induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen
复制标题
DOI：
10.1111/cea.12835
复制
发表时间：
2017-05-01
影响因子：
6.1
通讯作者：
Schiller, D.
中科院分区：
文献类型：
--
作者：
Groh, N.;von Loetzen, C. S.;Schiller, D.
背景：桦树花粉变应原特异性免疫治疗（AIT）产生Bet v 1特异性免疫球蛋白（IG）G（4），阻断IgE介导的超敏反应机制。目的分析15例（13/15例）急性免疫球蛋白（AIT）患者血清中IgE和IgG（4）抗体的表位特异性，并对15例（13/15例）AIT患者血清中IgE和IgG（4）抗体的表位特异性进行分析。通过圆二色谱和核磁共振光谱分析了重组（r）Bet v 1a和rBet v 1a（_11x）的结构排列，在5个潜在的表位中进行了修饰。通过ELISA和介体释放测定评估IgE与Betv 1的结合。用ELISA和western blot分析了抗Bet v 1a和血清IgE/IgG（4）的单克隆抗体与rBet v 1a的竞争性结合，以及血清抗体与非过敏性的Bet v 1型模式蛋白的竞争性结合。rBet v 1a（_11x）的单体分散是浓度和缓冲液依赖性的。rBet v 1a_（11 x）诱导的IgE介导的介质释放的EC_（50）增加了1500倍。在67%（10/15）的血清中，rBet v 1a_（11 x）结合的IgE和IgG（4）的降低相当。Bet v 1a特异性单克隆抗体对血清IgE和IgG（4）的结合抑制率分别为66.1%和64.9%。在33%（5/15）的血清中，血清IgE和IgG（4）特异性结合到由我们的模型蛋白质呈递的单个表位。结论和临床相关性接受AIT的患者产生Bet v 1a特异性IgG（4），其与IgE竞争部分相同或大部分重叠的表位。IgE和IgG表位的相似性（4）可能会刺激表位特异性诊断和治疗的发展。
Background Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G(4) which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG(4) specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG(4) antibodies are developed is under debate.Objective We sought to analyze the epitope specificities of IgE and IgG(4) antibodies from sera of patients who received AIT.Methods 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG(4) were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a(_11x), modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG(4) to rBet v 1a and serum antibody binding to a non-allergenic Bet v 1-type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot.Results rBet v 1a_(11x) had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a(__11x) was concentration and buffer-dependent. Up to 1500-fold increase in the EC50 for IgE-mediated mediator release induced by rBet v 1a_(11x) was determined. The reduction of IgE and IgG(4) binding to rBet v 1a_(11x) was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG(4) to 66.1% and 64.9%, respectively. Serum IgE and IgG(4) bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera.Conclusion and Clinical Relevance Patients receiving AIT develop Bet v 1a-specific IgG(4) which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG(4) might stimulate the development of epitope-specific diagnostics and therapeutics.