Definition of a pool of epitopes that recapitulates the T cell reactivity against major house dust mite allergens
Definition of a pool of epitopes that recapitulates the T cell reactivity against major house dust mite allergens
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DOI：
10.1111/cea.12507
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发表时间：
2015-10-01
影响因子：
6.1
通讯作者：
Sette, A.
中科院分区：
文献类型：
--
作者：
Hinz, D.;Oseroff, C.;Sette, A.
背景 屋尘螨 (HDM) 过敏原是哮喘的常见原因。来自 Dermatophagoides sp. 的 Der p 和 Der f。是人体强免疫原。过敏原提取物用于研究辅助性 T (Th2) 细胞对 HDM 的反应，这与过敏性疾病的发生和调节有关。 目的 定义一种表位混合物，在检测和表征 Th2 细胞反应方面可概括并可能替代 HDM 提取物。 方法 用 HDM 提取物刺激 52 名 HDM 过敏者和 10 名非过敏者的外周血单核细胞 (PBMC) 并进行测定包含一组 178 种肽，涵盖螨过敏原 Der p 1、2、23 组以及 Der f 1 和 2 组过敏原。汇集了本研究中和已发表文献中鉴定的最主要的 T 细胞表位库，并测试了离体 T 细胞反应。检查了与 HDM 特异性 IgE 滴度的相关性。结果 T 细胞对 Der p 和 Der f 衍生肽的反应性模式揭示了大量表位。免疫优势模式很明显，HDM 过敏原组 1 和 2 比组 23 占主导地位。此外，在给定抗原内，6-11 个表位占绝大多数反应。根据这些结果和已发表的数据，设计并发现了一个全面的尘螨表位池 (DMP)，可以检测离体 T 细胞反应。 DMP 离体反应性与 HDM 特异性 IgE 滴度相关，并且与常用的 HDM 提取物检测到的相似。离体 DMP 刺激与过敏供体中的主要 Th2 反应以及产生 IFN (I) over cap (3) I 3、IL17 和 IL10 的 T 细胞的次要反应性相关。结论和临床相关性 Der p 和 Der f 抗原的详细图谱定义了可用于检测离体 HDM 反应的表位库。
Background Allergens from house dust mites (HDM) are a common cause of asthma. Der p and Der f from Dermatophagoides sp. are strong immunogens in humans. Allergen extracts are used to study T helper (Th2) cell responses to HDM, which are implicated in the development and regulation of allergic disease.Objective To define an epitope mixture that recapitulates, and might substitute for, HDM extract in terms of detecting and characterizing Th2 cell responses.Methods Peripheral blood mononuclear cells (PBMC) from 52 HDM allergic and 10 non-allergic individuals were stimulated with HDM extracts and assayed with a set of 178 peptides spanning mite allergens group Der p 1, 2, 23 and Der f group 1 and 2 allergens. A pool of the most dominant T cell epitopes identified in the present study and from published literature was assembled and tested for ex vivo T cell responses. Correlation with HDM-specific IgE titres was examined.Results Patterns of T cell reactivity to Der p and Der f - derived peptides revealed a large number of epitopes. Clear patterns of immunodominance were apparent, with HDM allergen group 1 and 2 dominant over group 23. Furthermore, within a given antigen, 6-11 epitopes accounted for the vast majority of responses. Based on these results and published data, a comprehensive dust mite pool (DMP) of epitopes was designed and found to allow detection of ex vivo T cell responses. DMP ex vivo reactivity correlated with HDM-specific IgE titres and was similar to that detected with commonly used HDM extracts. Ex vivo DMP stimulation was associated with a predominant Th2 response in allergic donors, and minor reactivity of T cells producing IFN (I) over cap (3) I 3, IL17 and IL10.Conclusions & Clinical Relevance A detailed map of Der p and Der f antigens defined a pool of epitopes that can be used to detect ex vivo HDM responses.