Background

The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens.

Objectives

We sought to allow description of the complexity of IgE, IgG₄, and IgG epitope recognition at a global, allergome-wide level during allergen-specific immunotherapy (AIT).

Methods

We generated an allergome-wide microarray comprising 731 allergens in the form of more than 172,000 overlapping 16-mer peptides. Allergen recognition by IgE, IgG₄, and IgG was examined in serum samples collected from subjects undergoing AIT against pollen allergy.

Results

Extensive induction of linear peptide-specific Phl p 1– and Bet v 1–specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources.

Conclusions

The study highlights the complexity and subject-specific nature of allergen epitopes recognized following AIT. We envisage that epitope deconvolution will be an important aspect of future efforts to describe and analyze the outcomes of AIT in a personalized manner.

中文翻译：

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Allergome-wide 肽微阵列使过敏原特异性免疫治疗中的表位解卷积

背景

过敏原和过敏原特异性 IgE 的相互作用在效应细胞上的受体交联后引发过敏级联反应。其他同种型的抗体可以调节这种反应。受体交联需要抗体与过敏原上的多个表位结合。关于大多数过敏原表位结构的复杂性，可获得的信息有限。

目标

我们试图在过敏原特异性免疫治疗 (AIT) 期间，在全球、过敏原范围内描述 IgE、IgG ₄和 IgG 表位识别的复杂性。

方法

我们生成了一个包含 731 种过敏原的过敏原微阵列，其中包含超过 172,000 个重叠的 16 聚体肽。IgE、IgG ₄和 IgG 对过敏原的识别在从接受 AIT 花粉过敏的受试者收集的血清样品中进行了检查。

结果

Extensive induction of linear peptide-specific Phl p 1– and Bet v 1–specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources.

Conclusions

该研究强调了 AIT 后识别的过敏原表位的复杂性和受试者特异性。我们设想表位去卷积将成为未来以个性化方式描述和分析 AIT 结果的重要方面。