Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection.

Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection.
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DOI:
10.3389/fimmu.2015.00026
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发表时间:
2015
影响因子:
7.3
通讯作者:
Dunne DW
Dunne DW
中科院分区:
医学2区
文献类型:
--
作者:
Farnell EJ;Tyagi N;Ryan S;Chalmers IW;Pinot de Moira A;Jones FM;Wawrzyniak J;Fitzsimmons CM;Tukahebwa EM;Furnham N;Maizels RM;Dunne DW

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IgE反应与变态反应和对后生动物寄生虫的免疫有关。最近,我们假设,所有的环境过敏原承担结构同源性IgE结合抗原的后生动物寄生虫,这种同源性定义了相对较少的蛋白质家族含有过敏性目标。在这项研究中,已知的过敏原结构来自主要环境过敏原家族的Pfam结构域用于预测过敏原样蛋白。(SmProfilin、SmVAL-6、SmLipocalin、SmHSP 20、Sm磷酸丙糖异构酶、Sm硫氧还蛋白、Sm超氧化物歧化酶、Sm亲环蛋白和Sm磷酸甘油酸激酶)和非过敏原样[Sm动力蛋白轻链(SmDLC)、SmAldolase SmAK、SmUbiquitin和Sm 14 -3-3]蛋白。在大肠杆菌中产生重组抗原,并在感染S. mansoni在感染受试者中,所有过敏原样抗原均被IgE应答靶向,而对非过敏原样抗原、SmAK、Smubiquitin和Sm 14 -3-3的IgE应答基本上不存在,因为其流行率和幅度均较低。还发现了两个新的IgE结合Pfam结构域家族,以前未在过敏原家族数据库中描述,对SmDLC(PF 01221)和SmAldolase(PF 00274)具有普遍的IgE应答。最后,研究表明,与过敏原相关的免疫调节血清学过程也发生在对S. mansoni感染,包括在对IgE应答的人中产生IgG 4和对来自S.曼索尼鸡蛋。这项研究建立了已知的过敏原的结构,可用于预测IgE反应对同源寄生虫过敏原样分子(parallergens)和血清学反应与IgE/IgG 4 parallergens镜那些看到对过敏原,支持我们的假设,过敏性是植根于某些蛋白质结构域家族的后生动物寄生虫的表达。
The IgE response has been associated with both allergic reactions and immunity to metazoan parasites. Recently, we hypothesized that all environmental allergens bear structural homology to IgE-binding antigens from metazoan parasites and that this homology defines the relatively small number of protein families containing allergenic targets. In this study, known allergen structures (Pfam domains) from major environmental allergen families were used to predict allergen-like (SmProfilin, SmVAL-6, SmLipocalin, SmHSP20, Sm triosephosphate isomerase, SmThioredoxin, Sm superoxide dismutase, SmCyclophilin, and Sm phosphoglycerate kinase) and non-allergen-like [Sm dynein light chain (SmDLC), SmAldolase SmAK, SmUbiquitin, and Sm14-3-3] proteins in Schistosoma mansoni. Recombinant antigens were produced in Escherichia coli and IgG1, IgG4, and IgE responses against them measured in a cohort of people (n = 222) infected with S. mansoni. All allergen-like antigens were targeted by IgE responses in infected subjects, whilst IgE responses to the non-allergen-like antigens, SmAK, SmUbiquitin, and Sm14-3-3 were essentially absent being of both low prevalence and magnitude. Two new IgE-binding Pfam domain families, not previously described in allergen family databases, were also found, with prevalent IgE responses against SmDLC (PF01221) and SmAldolase (PF00274). Finally, it was demonstrated that immunoregulatory serological processes typically associated with allergens also occurred in responses to allergen-like proteins in S. mansoni infections, including the production of IgG4 in people responding with IgE and the down-regulation of IgE in response to increased antigen exposure from S. mansoni eggs. This study establishes that structures of known allergens can be used to predict IgE responses against homologous parasite allergen-like molecules (parallergens) and that serological responses with IgE/IgG4 to parallergens mirror those seen against allergens, supporting our hypothesis that allergenicity is rooted in expression of certain protein domain families in metazoan parasites.
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DOI: 10.1093/infdis/jis676
发表时间: 2013-01-15
期刊: The Journal of infectious diseases
影响因子: --
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通讯作者: Dunne DW