合成过敏原设计揭示了中等亲和力表位在肥大细胞脱颗粒中的重要性。
Synthetic allergen design reveals the significance of moderate affinity epitopes in mast cell degranulation.
机构信息
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.
出版信息
ACS Chem Biol. 2012 Nov 16;7(11):1796-801. doi: 10.1021/cb300193f. Epub 2012 Aug 21.
Abstract
This study describes the design of a well-defined homotetravalent synthetic allergen (HTA) system to investigate the effect of hapten-IgE interactions on mast cell degranulation. A library of DNP variants with varying affinities for IgE(DNP) was generated (K(d) from 8.1 nM to 9.2 μM), and 8 HTAs spanning this range were synthesized via conjugation of each DNP variant to the tetravalent scaffold. HTAs with hapten K(d) < 235 nM stimulated degranulation following a bell-shaped dose response curve with maximum response occurring near the hapten K(d). HTAs with hapten K(d) ≥ 235 nM failed to stimulate degranulation. To mimic physiological conditions, the percent of allergen specific IgE on cell surface was varied, and maximum degranulation occurred at 25% IgE(DNP). These results demonstrated that moderate hapten-IgE affinities are sufficient to trigger mast cell degranulation. Moreover, this study established the HTA design as a well-defined, controllable, and physiologically relevant experimental system to elucidate the mast cell degranulation mechanism.
摘要
本研究描述了一种设计良好的同四价合成变应原（HTA）系统，用于研究半抗原-IgE 相互作用对肥大细胞脱粒的影响。生成了具有不同 IgE（DNP）亲和力的 DNP 变体文库（K(d) 为 8.1 nM 至 9.2 μM），并通过将每种 DNP 变体连接到四价支架上来合成跨越此范围的 8 种 HTA。半抗原 K(d) < 235 nM 的 HTA 刺激脱粒，呈钟形剂量反应曲线，最大反应发生在半抗原 K(d)附近。半抗原 K(d)≥235 nM 的 HTA 未能刺激脱粒。为了模拟生理条件，改变细胞表面上的过敏原特异性 IgE 的百分比，并且最大脱粒发生在 25% IgE(DNP)。这些结果表明，中等的半抗原-IgE 亲和力足以触发肥大细胞脱粒。此外，本研究确立了 HTA 设计作为一种定义明确、可控和生理相关的实验系统，以阐明肥大细胞脱粒机制。
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