T Cell Reagent Research for Monitoring T Cell in Food Allergy

食物过敏（FA）现在是一个主要的公共卫生问题。食物过敏很常见——影响到8%的美国儿童——而且代价高昂——导致医疗保健系统和美国家庭每年花费约248亿美元。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跟踪fa特异性T细胞。我们假设，在整个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的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虾、牛奶和腰果过敏原的T细胞试剂有用的工具成为可能。此外，如果研究目标得以实现，我们将能够进一步了解虾、牛奶或腰果过敏的自然耐受性与持久性、治疗反应性与治疗难治性。基于我们之前在OIT方面的研究，我们提出了一项单一的临床研究，以获得新鲜血液样本来优化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，期间和之后对食物过敏患者的诊断，预后和机制使用。此外，我们将鉴定、表征和验证新的T细胞表位，用于以前未检测的重要食物过敏原，如牛奶、腰果和虾。我们将专注于表位鉴定和验证，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源性特征联系起来。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开创性的研究，以了解食物过敏的机制。为了推进这些目标，PI（纳多）将与dr。Pulendran,Chang,Davis,Elias,Chinthrajah,Maecker， Andorf和Desai。

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.