通过纳米过敏原鉴定主要屋尘螨过敏原 Der p 2 中的免疫原性表位。
Determination of immunogenic epitopes in major house dust mite allergen, Der p 2, via nanoallergens.
机构信息
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana; Berthiaume Institute for Precision Health, University of Notre Dame, Notre Dame, Indiana; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, Notre Dame, Indiana.
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana; Berthiaume Institute for Precision Health, University of Notre Dame, Notre Dame, Indiana; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, Notre Dame, Indiana; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana; Center for Rare & Neglected Diseases, University of Notre Dame, Notre Dame, Indiana.
出版信息
Ann Allergy Asthma Immunol. 2022 Aug;129(2):231-240.e2. doi: 10.1016/j.anai.2022.04.003. Epub 2022 Apr 9.
BACKGROUND
Despite the high prevalence of allergic asthma, currently, avoidance of the responsible allergens, which is nearly impossible for allergens such as house dust mite (HDM), remains among the most effective treatment. Consequently, determination of the immunogenic epitopes of allergens will aid in developing a better understanding of the condition for diagnostic and therapeutic purposes. Current methods of epitope identification, however, only evaluate immunoglobulin E-epitope binding interactions, which is not directly related to epitope immunogenicity.
OBJECTIVE
To determine and rank the immunogenicity of the epitopes of major HDM allergen, Der p 2.
METHODS
We performed degranulation assays with RBL-SX38 cells primed using patient plasma and challenged with nanoallergens which multivalently displayed epitopes to study the relative immunogenicity of various epitopes of Der p 2. Nanoallergens were used to evaluate epitopes individually or in combination.
RESULTS
When evaluated using 3 patient samples, 3 epitopes in 2 distal regions of Der p 2 were identified as highly immunogenic when presented in combination, whereas no individual epitope triggered relevant degranulation. One of the epitopes (69-DPNACHYMKCPLVKGQQY-86) was identified to be cooperatively immunogenic when combined with other epitopes.
CONCLUSION
Our study highlights the importance of conformational epitopes in HDM-related allergies. This study also provides further evidence of the versatility of nanoallergens and their value for functional characterization of allergy epitopes, by ranking the Der p 2 epitopes according to immunogenicity. We believe that nanoallergens, by aiding in identification and understanding of immunogenic epitopes, will provide a better understanding of the manifestation of the allergic condition and potentially aid in developing new treatments.
背景
尽管过敏性哮喘的患病率很高，但目前对于尘螨（HDM）等过敏原，避免接触仍是最有效的治疗方法之一。因此，确定过敏原的免疫原性表位将有助于为诊断和治疗目的更好地了解该疾病。然而，目前的表位鉴定方法仅评估免疫球蛋白 E-表位结合相互作用，而这与表位免疫原性并不直接相关。
目的
确定并排列主要 HDM 过敏原 Der p 2 的表位的免疫原性。
方法
我们使用经过患者血浆预致敏的 RBL-SX38 细胞进行脱颗粒测定，并使用多价展示表位的纳米过敏原进行挑战，以研究 Der p 2 的各种表位的相对免疫原性。纳米过敏原用于单独或组合评估表位。
结果
当使用 3 个患者样本进行评估时，在 Der p 2 的 2 个远端区域中鉴定出 3 个表位，当它们组合在一起时具有高度的免疫原性，而没有单个表位引发相关的脱颗粒。其中一个表位（69-DPNACHYMKCPLVKGQQY-86）与其他表位结合时被鉴定为协同免疫原性。
结论
我们的研究强调了 HDM 相关过敏中构象表位的重要性。本研究还进一步证明了纳米过敏原的多功能性及其用于功能表征过敏表位的价值，通过根据免疫原性对 Der p 2 表位进行排序。我们相信，纳米过敏原通过帮助识别和理解免疫原性表位，将更好地了解过敏状态的表现，并可能有助于开发新的治疗方法。
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