Allergen T cell epitopes and phenotypes in peanut allergy

花生过敏中的过敏原 T 细胞表位和表型

• 批准号: 10318131
• 负责人: William W. Kwok
• 金额: $ 34.38万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318131
• 关键词: Allergens; Allergic; Allergic Disease; Allergy to peanuts; Anaphylaxis; Biological Assay; Biological Markers; CCR6 gene; CD4 Positive T Lymphocytes; Cells; Clinical; Cytometry; Data Analyses; Development; Disease; Elements; Epitopes; Eragrostis; Flow Cytometry; Food Hypersensitivity; Frequencies; Functional disorder; Gene Expression; Gene Expression Profile; Helper-Inducer T-Lymphocyte; Heterogeneity; Hypersensitivity; IgE; Immunology; Immunotherapy; Individual; Knowledge; Link; Mediating; Molecular Profiling; Monitor; Pathogenesis; Phenotype; Play; Regulatory T-Lymphocyte; Role; Specificity; Stains; Stratification; Subgroup; System; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; TNFSF5 gene; Technology; Testing; Time; Up-Regulation; antigen-specific T cells; disease heterogeneity; effector T cell; functional disability; response; single-cell RNA sequencing; transcriptome sequencing; transcriptomics

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.

项目摘要-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。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CD 4 + T细胞在过敏原介导的疾病中起着重要的作用。 在疾病发展中的作用。本项目的目的是建立花生过敏作为一种异质性 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 本项目的主要内容包括：1）鉴定花生特异性CD 4 + T细胞表位; 2）检测花生特异性CD 4 + T细胞表型; 3）检测花生特异性CD 4 + T细胞表型。 花生表位特异性T辅助细胞; 3）测试花生特异性T细胞的表型 4）花生特异性辅助性T细胞表型异质性的评估 5）测试花生特异性T细胞的表型可以在花生过敏受试者中表达的假设; 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 和花生特异性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）测试调节性T细胞在过敏反应中的假说 受试者功能受损。 我们将使用II类四聚体追踪花生特定细胞和尖端技术，包括CyTOF 和单细胞RNA-seq，在检查花生特异性T细胞。还将开发CD 154/CD 137测定， 监测花生特异性T效应细胞和调节性T细胞。累积的结果将导致 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。