Allergen T cell epitopes and phenotypes in peanut allergy

项目概要 – 项目 1 花生过敏是一种常见的食物过敏，与致命的过敏反应有关。虽然过敏是一种 IgE 介导的疾病，越来越多的证据表明过敏原特异性 CD4 T 细胞发挥着重要作用 在疾病发展中的作用。该项目的目标是将花生过敏建立为异质性 使用花生表位特异性 T 细胞作为生物标志物来定义疾病异质性。具体目标 该项目将包括： 1) 鉴定花生特异性 CD4 T 细胞表位； 2) 检查表型 花生表位特异性T辅助细胞； 3）检验花生特异性T细胞表型的假设 取决于他们识别的表位； 4) 评估花生特异性T辅助细胞的表型异质性 花生过敏受试者的细胞； 5) 检验花生特异性 T 细胞表型可以被 用于将花生过敏受试者分为 2 种不同的亚型； 5) 建立表型之间的联系 花生特异性 T 细胞的分子特征和过敏性疾病状态； 6) 检查表位 特异性花生特异性调节性 T 细胞和 7) 检验调节性 T 细胞在过敏中的假设 受试者有功能障碍。 我们将使用 II 类四聚体来追踪花生特异性细胞和尖端技术，包括 CyTOF 和单细胞 RNA-seq，用于检查花生特异性 T 细胞。 CD154/CD137 检测也将被开发 监测花生特异性 T 效应细胞和调节性 T 细胞。累积的结果将带来很多 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.