Dissection of the IgE and T-cell recognition of the major group 5 grass pollen allergen Phl p 5.

Dissection of the IgE and T-cell recognition of the major group 5 grass pollen allergen Phl p 5.
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DOI:
10.1016/j.jaci.2013.08.038
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发表时间:
2014-03
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
通讯作者:
Valenta R
Valenta R
中科院分区:
其他
文献类型:
--
作者:
Focke-Tejkl M;Campana R;Reininger R;Lupinek C;Blatt K;Valent P;Pavkov-Keller T;Keller W;Valenta R

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主要的梯牧草花粉过敏原Phl p 5属于与花粉热和哮喘有关的最有效的过敏原。这项研究的特点是免疫显性IgE和T细胞识别位点的Phl p 5。七肽,P1至P7的长度为31至38个氨基酸,跨越的Phl p 5序列,合成,其特征在于圆二色光谱,并测试IgE反应性,嗜碱性粒细胞活化,和T细胞反应性。研究了载体结合肽在兔中诱导IgG抗体的能力,所述IgG抗体识别Phl p 5或来自不同草种的交叉反应性过敏原。测试肽特异性抗体抑制IgE对Phl p 5的反应性和过敏原诱导的过敏患者嗜碱性粒细胞活化的能力。这些肽没有显示二级结构,也没有显示IgE反应性或相关的变应原活性,表明Phl p 5 IgE表位是构象的。除P3外,肽特异性IgG抗体阻断IgE与过敏患者的Phl p 5结合,并与温带草交叉反应。IgE抑制实验和分子建模鉴定了Phl p 5的N-和C-末端结构域上的几个成簇的构象IgE表位。P4刺激患者最强的T细胞和细胞因子反应,不是主要IgE反应区域的一部分。我们的研究显示了一个有趣的主要IgE和T细胞反应域的解离在Phl p 5,这提供了一个基础的新形式的免疫治疗,选择性靶向IgE或T细胞反应的发展。
The major timothy grass pollen allergen Phl p 5 belongs to the most potent allergens involved in hay fever and asthma. This study characterized immune-dominant IgE- and T-cell–recognition sites of Phl p 5. Seven peptides, P1 to P7 with a length of 31 to 38 amino acids that spanned the Phl p 5 sequence, were synthesized, characterized by circular dichroism spectroscopy, and tested for IgE reactivity, basophil activation, and T-cell reactivity. Carrier-bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Phl p 5 or cross-reactive allergens from different grass species. Peptide-specific antibodies were tested for the capability to inhibit IgE reactivity to Phl p 5 and allergen-induced basophil activation of patients with allergy. The peptides exhibited no secondary structure and showed no IgE reactivity or relevant allergenic activity, indicating that Phl p 5 IgE epitopes are conformational. Except for P3, peptide-specific IgG antibodies blocked IgE binding to Phl p 5 of patients with allergy and cross-reacted with temperate grasses. IgE inhibition experiments and molecular modeling identified several clustered conformational IgE epitopes on the N- as well as C-terminal domain of Phl p 5. P4, which stimulated the strongest T-cell and cytokine responses in patients, was not part of the major IgE-reactive regions. Our study shows an interesting dissociation of the major IgE- and T-cell–reactive domains in Phl p 5 which provides a basis for the development of novel forms of immunotherapy that selectively target IgE or T-cell responses.
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