T Cell Reagent Research for Monitoring T Cell in Food Allergy

用于监测食物过敏 T 细胞的 T 细胞试剂研究

• 批准号: 10094186
• 负责人: Kari C. Nadeau
• 金额: $ 35.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-07 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10094186
• 关键词: ATAC-seq; Adult; Affect; Allergens; Allergic; Allergic Reaction; Antigens; Area; Bioinformatics; Biological Assay; Blood specimen; CD4 Positive T Lymphocytes; Cashew nut; Cells; Child; Chromatin; Clinical; Clinical Research; Clinical Trials; Computers; Control Groups; Data; Diagnostic; Ensure; Epitopes; Event; Family; Food; Food Hypersensitivity; Future; Gene Expression Profile; Health Expenditures; Healthcare Systems; Hypersensitivity; Immunophenotyping; Individual; Knowledge; Laboratories; Life; Milk; Monitor; National Institute of Allergy and Infectious Disease; Outcome; Participant; Patients; Pattern; Phase; Phenotype; Population; Prevention; Production; Prognostic Marker; Public Health; Publishing; Reagent; Refractory; Reporting; Reproducibility; Research; Research Personnel; Sampling; Scientist; Shrimp; Sorting - Cell Movement; T cell receptor repertoire sequencing; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; T-Lymphocyte Subsets; T-cell receptor repertoire; Technology; Testing; Validation; Work; antigen-specific T cells; base; clinical phenotype; cost; desensitization; design; experience; food allergen; learning algorithm; new therapeutic target; novel; oral immunotherapy; prognostic; success; time use; tool; transcriptome sequencing

Food allergy (FA) is now a major public health concern. Food allergy is both common—affecting ~8% of US children—and costly—resulting in ~$24.8 billion dollars per year in expenditures by the healthcare system and U.S. families. Approximately 40% of children with food allergy have experienced a severe, life-threatening allergic reaction, and 30% report allergies to multiple foods. Few studies have been conducted to track FA-specific T cells over time using epitopes and tetramer technology during the course of OIT. We hypothesize that distinctive patterns of T cell responses occur throughout OIT to shrimp or milk or cashew, and these can be revealed by immunophenotyping of cells responding to specific epitopes, including RNA-Seq assays, ATAC-Seq assays and TCR repertoire analyses. The results of the proposed studies will enable the production of useful tools for T cell reagents for shrimp, milk, and cashew allergens. Moreover, if the study aims are met, we will be able to further our knowledge of natural tolerance vs persistence vs treatment responsive vs treatment refractory shrimp, milk, or cashew allergy. Building upon our previous research in OIT, we propose a single clinical study to obtain fresh blood samples to optimize T cell reagent discovery and validation and, simultaneously, test the T cell reagent tools for their diagnostic, prognostic, and mechanistic use in food allergic patients before, during, and after OIT. Furthermore, we will identify, characterize, and validate new T cell epitopes for important food allergens not previously examined, such as milk, cashew, and shrimp. We will focus on epitope identification and validation, track the numbers and functions of epitope-specific T cells during stages of food allergy OIT, and then associate these parameters with careful phenotypic and endotypic characterizations in food allergic individuals. Our overall objectives are to conduct groundbreaking research in the areas of allergen epitope-specific T cell reagent identification and application to understanding mechanisms of food allergy. To advance these objectives, the PI(Nadeau) will work with Drs. Pulendran,Chang,Davis,Elias,Chinthrajah,Maecker, Andorf, and Desai.

食物过敏（FA）是一个主要的公共卫生问题。 食物过敏是常见的-影响约8%的美国儿童-和昂贵的-导致医疗保健系统和美国家庭每年约248亿美元的支出。 大约40%的食物过敏儿童经历过严重的、危及生命的过敏反应，30%的儿童报告对多种食物过敏。 在OIT过程中，很少有研究使用表位和四聚体技术随时间追踪FA特异性T细胞。 我们假设，在OIT中，对虾、牛奶或腰果的T细胞反应发生了独特的模式，这些可以通过对特定表位反应的细胞进行免疫表型分析来揭示，包括RNA-Seq测定、ATAC-Seq测定和TCR库分析。拟议研究的结果将使生产有用的工具，用于虾，牛奶和腰果过敏原的T细胞试剂。此外，如果达到研究目的，我们将能够进一步了解天然耐受性与持久性与治疗反应性与治疗难治性虾，牛奶或腰果过敏。基于我们以前在OIT中的研究，我们提出了一项单一的临床研究，以获得新鲜血液样本，以优化T细胞试剂的发现和验证，同时，测试T细胞试剂工具在OIT之前，期间和之后用于食物过敏患者的诊断，预后和机制。此外，我们将确定，表征和验证重要的食物过敏原，如牛奶，腰果和虾的新的T细胞表位。 我们将专注于表位识别和验证，跟踪表位特异性T细胞在食物过敏OIT阶段的数量和功能，然后将这些参数与食物过敏个体的表型和内型特征相关联。我们的总体目标是在过敏原表位特异性T细胞试剂鉴定和应用领域进行突破性研究，以了解食物过敏的机制。 为了推进这些目标，PI（Nadeau）将与Pulendran、Chang、Davis、Elias、Chinthrajah、Maecker、Andorf和Desai博士合作。