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首页> 外文期刊>Nature >Allergenicity Resulting From Functional Mimicry Of A Toll-like Receptor Complex Protein
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Allergenicity Resulting From Functional Mimicry Of A Toll-like Receptor Complex Protein

机译：Toll样受体复合蛋白的功能模仿导致的致敏性。

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Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins1. Although the proteins targeted by aeroallergic responses represent a tiny fraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon-the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house-dust-mite allergen, Der p 2, has structural homology with MD-2 (also known as LY96), the lipopolysaccharide (LPS)-binding component of the Toll-like receptor (TLR) 4 signalling complex. Here we show that Der p 2 also has functional homology, facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS-driven TLR4 signalling in the absence of MD-2. Mirroring this, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild type and MD-2-deficient, but not TLR4-deficient, mice. Our results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties. The fact that other members of the MD-2-like lipid-binding family are allergens, and that most defined major allergens are thought to be lipid-binding proteins5, suggests that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.
机译：空气过敏源于对普遍存在的，否则无害的环境蛋白的适应不良的免疫反应1。尽管以空气过敏反应为目标的蛋白质仅占人类所暴露的空气传播蛋白质的一小部分，但过敏原是一种相当普遍的现象-相同的蛋白质通常在整个人群中表现为空气过敏原。为什么特定的蛋白质倾向于在易感宿主中充当过敏原，这是一个基本的机械问题，至今仍未得到解答。主要的屋尘螨过敏原Der p 2与MD-2（也称为LY96）具有结构同源性，MD-2是Toll样受体（TLR）4信号复合物的脂多糖（LPS）结合成分。在这里，我们显示Der p 2也具有功能同源性，通过与TLR4复合体的直接相互作用促进信号传导，并在没有MD-2的情况下重构LPS驱动的TLR4信号传导。与此相吻合的是，气道致敏和Der p 2激发导致了野生型和MD-2缺陷型但不是TLR4缺陷型小鼠的实验性过敏性哮喘。我们的结果表明，Der p 2倾向于具有适应性免疫反应，因为它具有自动佐剂特性。 MD-2-like脂质结合家族的其他成员是过敏原，并且大多数定义的主要过敏原被认为是脂质结合蛋白5，这一事实表明这些蛋白及其伴随的脂质货物具有内在的佐剂活性。普遍性是致敏性现象的潜在机制。

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