Allergen T cell epitopes and phenotypes in peanut allergy

项目摘要-项目1 花生过敏是一种常见的食物过敏，与致命性过敏反应有关。虽然过敏是一种 IgE介导的疾病，越来越多的证据表明变应原特异的CD4T细胞发挥着显著的作用 在疾病发展中的作用。这个项目的目标是建立花生过敏作为一种异质性 以花生表位特异性T细胞作为定义疾病异质性的生物标志物的疾病。具体目标 该项目将包括：1)鉴定花生特有的CD4T细胞表位；2)检测花生的表型 花生表位特异性T辅助细胞；3)验证花生特异性T细胞表型的假设 4)花生特异性辅助性T细胞表型异质性的评估 花生过敏受试者中的细胞；5)检验花生特异性T细胞表型可以是 用于将花生过敏患者分为两个不同的亚型；5)建立表型之间的联系 花生特异性T细胞和过敏性疾病状态的分子特征；6)检测表位 花生特异性调节性T细胞和7)检验调节性T细胞在过敏性疾病中的假设 受试者的功能受损。 我们将使用第二类四聚体来追踪花生特定的细胞和尖端技术，包括CyTOF 以及单细胞RNA-seq，用于检测花生特异性T细胞。CD154/CD137检测也将被开发为 监控花生特异性T细胞和调节性T细胞。累积的结果将导致许多 更好地了解花生特异性T细胞在花生过敏发病机制中的作用。

Project Summary – Project 1 Peanut allergy is a common food allergy that is associated with fatal anaphylactic reaction. While allergy is an IgE mediated disease, accumulating evidence suggests that allergen specific CD4+ T cells play a significant role in disease development. The objective of this project is to establish peanut allergy as a heterogeneous disease with peanut epitope specific T cells as a biomarker to define disease heterogeneity. The specific aims of this project will include: 1) Identifying peanut specific CD4+ T cell epitope; 2) Examining the phenotype of peanut epitope specific T helper cells; 3) Testing the hypothesis that the phenotype of peanut specific T cells depends on the epitope they recognized; 4) Evaluating phenotype heterogeneity of peanut specific T helper cells in peanut allergic subjects; 5) Testing the hypothesis that phenotype of peanut specific T cells can be used to segregate peanut allergic subjects into 2 distinct subtypes; 5) Establishing a link between phenotype and molecular signature of peanut specific T cells and allergic disease status; 6) Examining the epitope specificity peanut specific regulatory T cells and 7) Testing the hypothesis that regulatory T cells in allergic subjects are functionally impaired. We will use class II tetramers in tracking peanut specific cell and cutting edge technologies, including CyTOF and single cell RNA-seq, in examining peanut specific T cells. A CD154/CD137 assay will also be developed to monitor both peanut specific T effectors and regulatory T cells. The cumulative results will lead to a much better understanding of peanut specific T cells in the pathogenesis of peanut allergy.