Allergen T cell epitopes and phenotypes during peanut immunotherapy

项目概要-项目2 我们的目的是探索花生表位特异性T细胞库在应答中出现的变化， 免疫疗法这项工作将利用一组食物过敏患者， 这些项目显示了对食物挑战和介入治疗的各种反应。 这些包括基线时临床表现不同的食物过敏患者， 治疗应答者，治疗期间发生不良反应的患者， 在治疗期间但不是在回避期结束时， 由于免疫疗法，对花生的长期耐受性。本次调查将在 免疫耐受网络资助的花生口服免疫治疗试验的背景下， Aravax资助的花生特异性肽免疫治疗试验的背景。效应T细胞和 调节性T细胞将被检查，我们将利用项目1的表位发现来探测 花生过敏原表位特异性T细胞拟议的工作将包括使用最先进的 技术，如pMHCII四聚体染色和双重CD 154/CD 137测定， 过敏原表位特异性T细胞对全球花生特异性T细胞反应的贡献。 我们还将探讨TCR库和转录表型的改变， 花生特异性T细胞在临床干预。这些信息与确定 合适的靶点来指导最佳过敏疫苗的设计。我们将最终确定范围 这些T细胞表位可以用作生物标志物，预测哪些患者最有可能 受益于这些治疗干预，免疫机制参与和筛选 免疫疗法可能导致不必要风险的候选人。

PROJECT SUMMARY – Project 2 We aim to explore the alterations that arise on peanut epitope-specific T-cell repertoires in response to immunotherapy. This work will take advantage of a cohort of food allergy patients, available to this project, that display a wide variety of responses to food challenge and to interventional therapy. These include food allergic patients who differ in clinical manifestation at baseline, patient non- responder to therapy, patients who experience adverse reactions during therapy, patients that loss peanut sensitization during therapy but not at the end of an avoidance period and patient that gain long term tolerance to peanut as a result of immunotherapy. This investigation will be performed in the context of an Immune Tolerance Network funded Peanut Oral Immunotherapy trial and in the context of an Aravax funded peanut specific peptide immunotherapy trial. Both effector T cells and regulatory T cells will be examined and we will capitalize on epitope discovery from project 1 to probe peanut allergen epitope specific T cells. The proposed work will include the use of state-of art technologies such as pMHCII tetramer staining and dual CD154/CD137 assay allowing determination of the contribution of allergen epitope-specific T cells to the global peanut specific T cell responses. We will also explore the alterations that arise on TCR repertoire and transcriptional phenotype of peanut-specific T cells during clinical intervention. These information are pertinent for determining suitable target to guide the design of optimal allergy vaccines. We will finally determine the extent to which these T cell epitopes can be used as biomarker predicting which patients are most likely to benefit from these therapeutic interventions, which immune mechanisms are involved and screen out those candidates in whom immunotherapy may lead to unnecessary risks.