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对主要艾蒿花粉过敏原Art v 1的T细胞反应由一个表位主导。

The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope.

作者信息

Jahn-Schmid Beatrice, Kelemen Peter, Himly Martin, Bohle Barbara, Fischer Gottfried, Ferreira Fatima, Ebner Christof

机构信息

Department of Pathophysiology, Division of Immunopathology, University of Vienna, AKH-3Q, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

出版信息

J Immunol. 2002 Nov 15;169(10):6005-11. doi: 10.4049/jimmunol.169.10.6005.

Abstract

Mugwort (Artemisia vulgaris) pollen allergens represent the main cause of pollinosis in late summer in Europe. At least 95% of sera from mugwort pollen-allergic patients contain IgE against a highly glycosylated 24- to 28-kDa glycoprotein. Recently, this major allergen, termed Art v 1, was characterized, cloned in Escherichia coli, and produced in recombinant form. In the present study we characterized and compared the T cell responses to natural (nArt v 1) and recombinant Art v 1 (rArt v 1). In vitro T cell responses to nArt v 1 and rArt v 1 were studied in PBMC, T cell lines (TCL), and T cell clones (TCC) established from PBMC of mugwort-allergic patients. Stimulation of PBMC or allergen-specific TCL with either nArt v 1 or rArt v 1 resulted in comparable proliferative T cell responses. Eighty-five percent of the TCC reactive with rArt v 1 cross-reacted with the natural protein. The majority of the CD4(+)CD8(-)TCR alphabeta(+) Art v 1-specific TCC, obtained from 10 different donors, belonged to the Th2 phenotype. Epitope mapping of TCL and TCC using overlapping peptides revealed a single immunodominant T cell epitope recognized by 81% of the patients. Inhibition experiments demonstrated that the presentation of this peptide is restricted by HLA-DR molecules. In conclusion, the T cell response to Art v 1 is characterized by one strong immunodominant epitope and evidently differs from the T cell responses to other common pollen allergens known to contain multiple T cell epitopes. Therefore, mugwort allergy may be an ideal candidate for a peptide-based immunotherapy approach.

摘要

艾蒿(Artemisia vulgaris)花粉过敏原是欧洲夏末花粉症的主要病因。至少95%的艾蒿花粉过敏患者血清中含有针对一种高度糖基化的24至28 kDa糖蛋白的IgE。最近,这种主要过敏原被命名为Art v 1,已得到鉴定,在大肠杆菌中克隆,并以重组形式产生。在本研究中,我们鉴定并比较了对天然(nArt v 1)和重组Art v 1(rArt v 1)的T细胞反应。在从艾蒿过敏患者外周血单核细胞(PBMC)建立的T细胞系(TCL)和T细胞克隆(TCC)中,研究了体外对nArt v 1和rArt v 1的T细胞反应。用nArt v 1或rArt v 1刺激PBMC或过敏原特异性TCL,可产生相当的T细胞增殖反应。85%与rArt v 1反应的TCC与天然蛋白发生交叉反应。从10个不同供体获得的大多数CD4(+)CD8(-)TCR alphabeta(+) Art v 1特异性TCC属于Th2表型。使用重叠肽对TCL和TCC进行表位作图,发现了一个单一的免疫显性T细胞表位,81%的患者可识别该表位。抑制实验表明,该肽的呈递受HLA-DR分子限制。总之,对Art v 1的T细胞反应以一个强免疫显性表位为特征,明显不同于对其他已知含有多个T细胞表位的常见花粉过敏原的T细胞反应。因此,艾蒿过敏可能是基于肽的免疫治疗方法的理想候选对象。

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