Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein.
Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein.
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由 Toll 样受体复合蛋白的功能模拟引起的过敏性。
DOI：
10.1038/nature07548
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发表时间：
2009-01-29
期刊：
影响因子：
64.8
通讯作者：
Karp, Christopher L.
中科院分区：
文献类型：
--
作者：
Trompette, Aurelien;Divanovic, Senad;Visintin, Alberto;Blanchard, Carine;Hegde, Rashmi S.;Madan, Rajat;Thorne, Peter S.;Wills-Karp, Marsha;Gioannini, Theresa L.;Weiss, Jerry P.;Karp, Christopher L.
空气变态反应是由于对普遍存在的、原本无害的环境蛋白质的适应不良免疫反应。虽然这些蛋白质只占人类接触的空气中蛋白质的一小部分，但过敏性是一个相当普遍的现象相同的蛋白质在整个人群中通常表现为空气过敏原。为什么特定的蛋白质倾向于在易感宿主中作为过敏原是一个基本的机制问题，在很大程度上仍然没有答案。主要的屋尘螨过敏原Der p 2与Toll样受体（TLR）4信号复合物的脂多糖（LPS）结合组分MD-2具有结构同源性。在这里，我们表明，Der p 2具有功能同源性，以及，促进信号通过直接与TLR 4复合物的相互作用，并重建LPS驱动的TLR 4信号在MD-2的情况下。由此可见，气道致敏和用Der p 2激发导致野生型和MD-2缺陷型小鼠的实验性过敏性哮喘，但不导致TLR 4缺陷型小鼠。我们的研究结果表明，Der p 2往往是适应性免疫反应的目标，因为它的自身佐剂特性。MD-2样脂质结合家族的其他成员是过敏原，并且大多数确定的主要过敏原被认为是脂质结合蛋白，这一事实表明，这些蛋白质及其伴随的脂质货物的内在佐剂活性可能具有一定的普遍性，作为过敏性现象的基础机制。
Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins. While the proteins so targeted 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 major house dust mite allergen, Der p 2, has structural homology with MD-2, the lipopolysaccharide (LPS)-binding component of the Toll-like receptor (TLR)4 signalling complex. Here we show that Der p 2 has functional homology as well, 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 suggest 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 a majority of defined major allergens are thought to be lipid-binding proteins, 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.
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影响因子：
30.5
作者：
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