A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help

Meena Narayanan, Raphaela Freidl, M. Focke‐Tejkl, U. Baranyi, T. Wekerle, R. Valenta, B. Linhart
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引用次数: 11

Abstract

More than 40% of allergic patients suffer from grass pollen allergy. Phl p 1, the major timothy grass pollen allergen, belongs to the cross-reactive group 1 grass pollen allergens that are thought to initiate allergic sensitization to grass pollen. Repeated allergen encounter boosts allergen-specific IgE production and enhances clinical sensitivity in patients. To investigate immunological mechanisms underlying the boosting of allergen-specific secondary IgE Ab responses and the allergen epitopes involved, a murine model for Phl p 1 was established. A B cell epitope–derived peptide of Phl p 1 devoid of allergen-specific T cell epitopes, as recognized by BALB/c mice, was fused to an allergen-unrelated carrier in the form of a recombinant fusion protein and used for sensitization. This fusion protein allowed the induction of allergen-specific IgE Ab responses without allergen-specific T cell help. Allergen-specific Ab responses were subsequently boosted with molecules containing the B cell epitope–derived peptide without carrier or linked to other allergen-unrelated carriers. Oligomeric peptide bound to a carrier different from that which had been used for sensitization boosted allergen-specific secondary IgE responses without a detectable allergen-specific T cell response. Our results indicate that allergen-specific secondary IgE Ab responses can be boosted by repetitive B cell epitopes without allergen-specific T cell help by cross-linking of the B cell epitope receptor. This finding has important implications for the design of new allergy vaccines.
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草花粉过敏原php1衍生的B细胞表位肽在没有过敏原特异性T细胞帮助的情况下增强过敏原特异性二抗反应
超过40%的过敏患者患有草花粉过敏。php1是主要的草花粉过敏原,属于交叉反应的1族草花粉过敏原,被认为是对草花粉的过敏致敏。反复接触过敏原会促进过敏原特异性IgE的产生,提高患者的临床敏感性。为了研究增强过敏原特异性继发性IgE Ab反应的免疫学机制和所涉及的过敏原表位,我们建立了小鼠php1模型。BALB/c小鼠识别的缺乏过敏原特异性T细胞表位的B细胞源性php1肽,以重组融合蛋白的形式与过敏原无关的载体融合,并用于致敏。这种融合蛋白允许在没有过敏原特异性T细胞帮助的情况下诱导过敏原特异性IgE Ab反应。随后,含有B细胞表位衍生肽的分子(无载体或与其他与过敏原无关的载体相连)增强了过敏原特异性Ab反应。寡聚肽结合的载体不同于已用于致敏的载体增强了过敏原特异性继发性IgE反应,而没有检测到过敏原特异性T细胞反应。我们的研究结果表明,重复的B细胞表位可以促进过敏原特异性的继发性IgE Ab反应,而无需过敏原特异性T细胞通过B细胞表位受体交联的帮助。这一发现对设计新的过敏疫苗具有重要意义。
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