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结合载体的非变应原性 Der p 2 肽诱导 IgG 抗体,阻断变应原诱导的过敏患者嗜碱性粒细胞活化。

Carrier-bound nonallergenic Der p 2 peptides induce IgG antibodies blocking allergen-induced basophil activation in allergic patients.

机构信息

Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

出版信息

Allergy. 2012 May;67(5):609-21. doi: 10.1111/j.1398-9995.2012.02794.x. Epub 2012 Feb 17.

Abstract

BACKGROUND

More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT).

METHODS

Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients.

RESULTS

Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2.

CONCLUSIONS

Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.

摘要

背景

超过 90%的屋尘螨过敏患者对主要过敏原屋尘螨变应原 2(Der p 2)敏感。本研究旨在开发并鉴定基于载体结合 Der p 2 肽的变应原疫苗,以减少特异性免疫治疗(SIT)过程中 IgE 和 T 细胞介导的副作用。

方法

合成了 5 个 Der p 2 肽(P1-P5),并对其 IgE 反应性和变应原活性进行了分析。从尘螨过敏患者的外周血单核细胞中测定 Der p 2 和 Der p 2 肽诱导的淋巴细胞增殖和细胞因子反应。在小鼠和兔中用载体结合的 Der p 2 肽诱导的 Der p 2 特异性 IgG 抗体,检测其在过敏患者中抑制 IgE 结合和嗜碱性粒细胞活化的能力。

结果

在覆盖 Der p 2 序列的 5 个重叠肽(P1-P5)中,确定了 2 个肽(P2 和 P4),它们没有表现出明显的 IgE 反应性、变应原活性,并且诱导的 Der p 2 特异性 T 细胞活化低于 Der p 2。然而,当与载体结合时,P2 和 P4 在动物中诱导产生 Der p 2 特异性 IgG 抗体,这些抗体抑制过敏患者的 IgE 与过敏原结合,并抑制过敏原诱导的嗜碱性粒细胞活化,与用 Der p 2 诱导的抗体相似。

结论

载体结合的 Der p 2 肽可以避免 IgE 介导的副作用,并且由于其激活过敏原特异性 T 细胞的潜力较低,它们可能会减少 SIT 过程中的迟发性副作用。此外,这些肽也可能对预防性疫苗接种有用。

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