Allergen T cell epitopes and phenotypes during peanut immunotherapy

项目摘要--项目2 我们的目标是探索花生表位特异性T细胞谱系的变化。 去接受免疫治疗。这项工作将利用食物过敏患者的队列， 该项目展示了对食物挑战和介入治疗的各种反应。 这些患者包括在基线时临床表现不同的食物过敏患者，患者非 治疗的应答者，在治疗过程中经历不良反应的患者，失去治疗的患者 花生在治疗期间致敏，但不是在避孕期结束时和患者获得的收益 免疫治疗对花生的长期耐受性。这项调查将在#年进行 免疫耐受网络资助的花生口服免疫治疗试验的背景和 一项由Aravax资助的花生特异性多肽免疫治疗试验的背景。效应器T细胞和 将检查调节性T细胞，我们将利用项目1中发现的表位来进行探测 花生变应原表位特异性T细胞。拟议的工作将包括使用最先进的技术 PMHCII四聚体染色和双CD154/CD137检测技术 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。 我们还将探索在TCR谱系和转录表型上出现的变化 花生特异性T细胞在临床干预中的作用。这些信息与确定 合适的靶点来指导最佳过敏疫苗的设计。我们将最终确定到什么程度 哪些T细胞表位可以作为生物标志物来预测哪些患者最有可能 从这些治疗干预中受益，并筛选出涉及哪些免疫机制 那些免疫治疗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.