Hinz D, Oseroff C, Pham J, Sidney J, Peters B, Sette A
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Clin Exp Allergy. 2015 Oct;45(10):1601-12. doi: 10.1111/cea.12507.
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.
To define an epitope mixture that recapitulates, and might substitute for, HDM extract in terms of detecting and characterizing Th2 cell responses.
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.
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 IFNγ, 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.
屋尘螨(HDM)过敏原是哮喘的常见病因。来自嗜皮螨属的Der p和Der f是人类强烈的免疫原。过敏原提取物用于研究T辅助(Th2)细胞对HDM的反应,这与过敏性疾病的发生和调节有关。
确定一种表位混合物,该混合物在检测和表征Th2细胞反应方面能够概括HDM提取物,并可能替代HDM提取物。
用HDM提取物刺激52名HDM过敏个体和10名非过敏个体的外周血单个核细胞(PBMC),并用一组178种肽进行检测,这些肽涵盖螨过敏原Der p 1、2、23组以及Der f 1和2组过敏原。汇集本研究和已发表文献中鉴定出的最主要的T细胞表位,并检测其体外T细胞反应。检查与HDM特异性IgE滴度的相关性。
T细胞对Der p和Der f衍生肽的反应模式显示出大量表位。明显的免疫显性模式很明显,HDM过敏原1组和2组比23组占优势。此外,在给定抗原中,6-11个表位占绝大多数反应。基于这些结果和已发表的数据,设计了一种综合尘螨表位库(DMP),发现其能够检测体外T细胞反应。DMP体外反应性与HDM特异性IgE滴度相关,并且与常用HDM提取物检测到的反应性相似。在过敏供体中,体外DMP刺激与主要的Th2反应相关,并且产生IFNγ、IL17和IL10的T细胞反应较弱。
Der p和Der f抗原的详细图谱确定了一组可用于检测体外HDM反应的表位。