Streeter Heather B, Lucas Lora G, West Robert M, Krishna Mamidipudi T, Wraith David C
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom.
Front Immunol. 2025 Apr 11;16:1569283. doi: 10.3389/fimmu.2025.1569283. eCollection 2025.
Peptides were designed to induce immune tolerance to the major antigen associated with house dust mite (HDM) allergy, Der p 1. HDM is commonly associated with allergic responses in allergic rhinitis and asthma, with Der p 1 specific T-cells implicated in ongoing disease. Tolerogenic peptide immunotherapy can induce tolerance in pathogenic T-cells, bypass mast cell activation and hence reduce the risk of anaphylaxis. A pan-DR binding epitope of Der p 1, covering the broad population, was tested for efficacy in HLA-DR transgenic mice.
Potential pan-HLA-DR binding tolerogenic T-cell epitopes from Der p 1 were predicted and manufactured (synthetic peptides A-E). Participants included HDM sensitised (allergic rhinitis/asthma, n=25), non-HDM sensitised (atopic controls sensitised to ≥1 other aero-allergens, n=10) and non-atopic healthy controls, n=10). Peripheral blood mononuclear cells (PBMC) were collected and screened for immune responses to Der p 1 or test peptides A-E. Mapping of minimal T-cell epitopes, apitope (antigen-processing independent epitope) validation and tolerance induction were tested in HLA-DR transgenic mice.
HDM-sensitised subjects have an elevated response to pan-DR binding peptide D 30mer. Peptide analogue D121B, containing the minimal epitope and optimised for solubility, was verified as a tolerogenic apitope and induced tolerance against Der p 1 antigens in HLA-DR4 transgenic mice .
A tolerogenic peptide, apitope D121B, reduces T-cell immune responses to Der p 1 and is a promising candidate for further development as an immunotherapy for HDM-associated allergic rhinitis and asthma.
设计肽以诱导对与屋尘螨（HDM）过敏相关的主要抗原Der p 1的免疫耐受。HDM通常与过敏性鼻炎和哮喘中的过敏反应相关，Der p 1特异性T细胞与疾病进展有关。耐受性肽免疫疗法可诱导致病性T细胞产生耐受，绕过肥大细胞激活，从而降低过敏反应的风险。在HLA-DR转基因小鼠中测试了Der p 1的一种泛DR结合表位，该表位覆盖广泛人群。
预测并制备了来自Der p 1的潜在泛HLA-DR结合耐受性T细胞表位（合成肽A-E）。参与者包括HDM致敏者（过敏性鼻炎/哮喘，n = 25）、非HDM致敏者（对≥1种其他空气过敏原致敏的特应性对照，n = 10）和非特应性健康对照（n = 10）。收集外周血单核细胞（PBMC），并筛选其对Der p 1或测试肽A-E的免疫反应。在HLA-DR转基因小鼠中测试最小T细胞表位的定位、apitope（抗原加工非依赖性表位）验证和耐受性诱导。
HDM致敏受试者对泛DR结合肽D 30聚体的反应增强。含有最小表位并针对溶解性进行优化的肽类似物D121B被确认为耐受性apitope，并在HLA-DR4转基因小鼠中诱导了对Der p 1抗原的耐受。
耐受性肽apitope D121B可降低T细胞对Der p 1的免疫反应，是作为HDM相关过敏性鼻炎和哮喘免疫疗法进一步开发的有前景的候选物。
