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，与致命的过敏反应有关。虽然过敏是 IgE介导的疾病，积累的证据表明过敏原特异性CD4+ T细胞起着显着的 在疾病发展中的作用。该项目的目的是建立花生过敏为异质 花生表位特异性T细胞的疾病是定义疾病异质性的生物标志物。具体目标 该项目将包括：1）识别花生特异性CD4+ T细胞表位； 2）检查表型 花生表位特异性T辅助细胞； 3）测试假设花生特异性T细胞的表型 取决于他们认识到的情节； 4）评估花生特异性T助手的表型异质性 花生过敏受试者中的细胞； 5）检验假设花生特有T细胞的表型可以是 用于将花生过敏的受试者隔离为2个不同的亚型； 5）在表型之间建立联系 和花生特异性T细胞的分子特征和过敏性疾病状况； 6）检查表位 特异性花生特异性调节T细胞和7）检验了过敏性调节性T细胞的假设 受试者在功能上受损。 我们将使用II类四聚体在跟踪花生特异性细胞和尖端技术，包括细胞 和单细胞RNA-seq，在检查花生特异性T细胞时。 CD154/CD137分析也将开发为 监测花生特异性T效应和调节T细胞。累积结果将导致很多 在花生过敏的发病机理中更好地了解花生特异性T细胞。