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来自巴西日圆线虫的一种可被特异性IgE识别的新型抗原的鉴定与表征。

Identification and characterization of a novel antigen from the nematode Nippostrongylus brasiliensis recognized by specific IgE.

作者信息

Pochanke Veronika, Koller Samuel, Dayer Régine, Hatak Sarah, Ludewig Burkhard, Zinkernagel Rolf M, Hengartner Hans, McCoy Kathy D

机构信息

Institute for Experimental Immunology, University Hospital Zürich, Zürich, Switzerland.

出版信息

Eur J Immunol. 2007 May;37(5):1275-84. doi: 10.1002/eji.200737135.

Abstract

Identification and characterization of IgE-inducing antigens are important for elucidating the mechanisms involved in IgE-mediated immune responses in allergic diseases and parasite infections. While many allergens have been characterized, little is known about parasite antigens inducing specific IgE following infection. In order to identify antigens from the nematode Nippostrongylus brasiliensis, we generated an IgE-producing B cell hybridoma from N. brasiliensis-infected C57BL/6 mice and constructed a cDNA phage display library from N. brasiliensis. We successfully cloned and expressed an N. brasiliensis antigen (Nb-Ag1) that showed specific binding to anti-N. brasiliensis IgE. Nb-Ag1 localized to the pharynx of adult N. brasiliensis, suggesting that Nb-Ag1 is a potential pharyngeal gland antigen. Nb-Ag1-specific IgE could be detected in the serum of N. brasiliensis-infected mice, but only for a short time and only following a challenge infection. In contrast, local administration of Nb-Ag1 during primary, secondary and tertiary infections induced Nb-Ag1-specific IgE-mediated active cutaneous anaphylaxis. Therefore, amongst the high amounts of polyclonal total IgE, low levels of parasite-specific IgE responses are induced during primary helminth infections. Here, we show that even such low levels of parasite-specific IgE are sufficient to prime mast cells in vivo and mediate degranulation.

摘要

鉴定和表征诱导IgE的抗原对于阐明过敏性疾病和寄生虫感染中IgE介导的免疫反应所涉及的机制至关重要。虽然许多过敏原已被表征,但对于感染后诱导特异性IgE的寄生虫抗原却知之甚少。为了从巴西日圆线虫中鉴定抗原,我们从感染巴西日圆线虫的C57BL/6小鼠中产生了产生IgE的B细胞杂交瘤,并构建了巴西日圆线虫的cDNA噬菌体展示文库。我们成功克隆并表达了一种巴西日圆线虫抗原(Nb-Ag1),它显示出与抗巴西日圆线虫IgE的特异性结合。Nb-Ag1定位于成年巴西日圆线虫的咽部,表明Nb-Ag1是一种潜在的咽腺抗原。在感染巴西日圆线虫的小鼠血清中可以检测到Nb-Ag1特异性IgE,但仅在短时间内且仅在激发感染后才能检测到。相比之下,在初次、二次和三次感染期间局部给予Nb-Ag1会诱导Nb-Ag1特异性IgE介导的主动皮肤过敏反应。因此,在大量的多克隆总IgE中,初次蠕虫感染期间诱导的寄生虫特异性IgE反应水平较低。在这里,我们表明,即使是如此低水平的寄生虫特异性IgE也足以在体内启动肥大细胞并介导脱颗粒。

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