Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum München, Research Center for Environmental Health, Augsburg, Germany; CK CARE Christine Kühne Center for Allergy Research and Education, Davos, Switzerland.
J Allergy Clin Immunol. 2018 Sep;142(3):984-987.e6. doi: 10.1016/j.jaci.2018.05.004. Epub 2018 May 18.
Over 100 million people worldwide suffer from birch pollen allergy. However, identification of molecular determinants driving Th2-biased allergic sensitization to Bet v 1, the major birch pollen allergen, remains elusive.
Here, we examined whether Bet v 1 or the pollen matrix is responsible for activation of antigen-presenting cells and the subsequent Th2 polarization, relevant in the process of allergic sensitization.
The allergenicity of Bet v 1 and of birch pollen extract (BPE) was addressed by stimulation of murine and human dendritic cells and by in vivo monitoring of Th2 polarization. Further, Bet v 1 was depleted from BPE by immunoprecipitation in order to analyze its involvement in the occurrence of a Th2 response.
The allergen alone did neither stimulate dendritic cells in vitro nor induced Th2 polarization in vivo, even in the presence of the natural LPS concentration determined in the BPE. In contrast, BPE was shown to activate dendritic cells and strongly promoted a Th2 polarization. Even upon immunization with Bet v 1-depleted BPE the amount of induced Th2 cells remained unaltered.
This finding indicates that the Th2-polarizing potential of BPE is Bet v 1 independent; therefore, sensitization to Bet v 1 is induced by an as-yet-undetermined pollen compound or mechanism in the pollen environment. These data suggest that sensitization is not exclusively linked to the intrinsic properties of individual proteins. These findings are relevant in understanding allergic sensitization towards pollen allergens and might pave the way for future prophylactic approaches.
全世界有超过 1 亿人患有桦树花粉过敏症。然而，导致主要桦树花粉过敏原 Bet v 1 产生 Th2 偏向性过敏致敏的分子决定因素仍难以确定。
本研究旨在探讨 Bet v 1 或花粉基质是否负责激活抗原呈递细胞，以及随后的 Th2 极化，这与过敏致敏过程相关。
通过刺激鼠类和人类树突状细胞，并通过体内监测 Th2 极化，研究了 Bet v 1 和桦树花粉提取物（BPE）的变应原性。此外，通过免疫沉淀从 BPE 中去除 Bet v 1，以分析其在 Th2 反应发生中的作用。
单独的过敏原既不能在体外刺激树突状细胞，也不能在体内诱导 Th2 极化，即使存在 BPE 中确定的天然 LPS 浓度也是如此。相比之下，BPE 被证明可以激活树突状细胞，并强烈促进 Th2 极化。即使使用去除了 Bet v 1 的 BPE 进行免疫接种，诱导的 Th2 细胞数量也没有改变。
这一发现表明 BPE 的 Th2 极化潜力与 Bet v 1 无关；因此，对 Bet v 1 的致敏是由花粉环境中的未知花粉化合物或机制引起的。这些数据表明，致敏不仅仅与单个蛋白质的固有特性有关。这些发现对于理解花粉过敏原的过敏致敏具有重要意义，并可能为未来的预防性方法铺平道路。
