Allergen T cell epitopes and phenotypes in peanut allergy and immunotherapy

花生过敏和免疫治疗中的过敏原 T 细胞表位和表型

• 批准号: 10318122
• 负责人: William W. Kwok
• 金额: $ 101.66万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318122
• 关键词: Address; Adverse event; Adverse reactions; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Anaphylaxis; Benefits and Risks; Biological Assay; Biological Markers; CD4 Positive T Lymphocytes; Cells; Characteristics; Child; Chronic; Clinical; Clinical Treatment; Clinical Trials; Cytometry; Data Analyses; Development; Disease; Dose; Environment; Epitopes; Equipment; Feedback; Flow Cytometry; Food; Food Hypersensitivity; Frequencies; Future; Gene Expression; Goals; Heterogeneity; Hypersensitivity; IgE; Immune System Diseases; Immune response; Immunologic Monitoring; Immunology; Immunotherapy; Individual; Infrastructure; Interleukin-10; Interleukin-4; Intervention; Knowledge; Lead; Metals; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Peptide Vaccines; Peptides; Phenotype; Prevalence; Protocols documentation; Reagent; Regulatory T-Lymphocyte; Research Institute; Research Support; Role; Sampling; Solid; Specificity; Stains; Symptoms; System; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; T-Lymphocyte Subsets; TNFSF5 gene; Technology; Testing; Th2 Cells; Treatment outcome; Vaccines; Work; antigen-specific T cells; clinical application; combinatorial; data integration; data management; desensitization; design; effector T cell; exhaust; food antigen; immunotherapy clinical trials; immunotherapy trials; insight; intradermal injection; novel; oral immunotherapy; patient stratification; precision medicine; recruit; response; single-cell RNA sequencing; therapeutic target; tool; transcriptome sequencing; treatment response; vaccine immunotherapy; vaccine trial

Summary for Overview The proposed Center will perform mechanistic studies of allergen-specific T cell responses in peanut allergic subjects through two synergistic projects. The first project will investigate the phenotypic and functional characteristics of allergen specific T cells in subjects with peanut allergy and subjects that are tolerant to peanut. The second project will investigate changes in the frequency, phenotype, and function of allergen- specific T cells that are associated with immunotherapy. This project will utilize longitudinal clinical samples from a peanut oral immunotherapy trial and samples from a peanut peptide immunotherapy in which subjects will receive intradermal injection of the peanut peptide vaccine. Both projects will utilize cutting edge technologies including metal tag class II tetramer reagents with CyTOF and single cell RNA-seq to study peanut allergen specific T cells. The infrastructure of our Center includes two cores. Core A, the Administrative Core, will oversee scientific progress of the two projects, facilitate data integration between the projects, and provide managerial responsibility and fiscal management for the Center. Core B, the Gene Expression and Systems Immunology Core will be responsible for data analysis for RNA-seq, Flow Cytometry and Mass Cytometry, and will also work with Core A in data management. Benaroya Research Institute has state-of-the- art facilities and technical equipment, established infrastructure for technical support and subject recruitment, and collegial environments to support the research as propose.

概述摘要 该中心将在花生过敏性疾病中进行过敏原特异性T细胞反应的机制研究。 通过两个协同项目。第一个项目将调查表型和功能 花生过敏受试者和对花生过敏耐受的受试者中过敏原特异性T细胞的特征 花生第二个项目将研究过敏原的频率、表型和功能的变化， 与免疫疗法相关的特异性T细胞。本项目将利用纵向临床样本 来自花生口服免疫疗法试验的样品和来自花生肽免疫疗法的样品，其中受试者 将接受皮内注射花生肽疫苗。这两个项目都将利用尖端技术 技术，包括金属标签II类四聚体试剂与CyTOF和单细胞RNA-seq研究 花生过敏原特异性T细胞我们中心的基础设施包括两个核心。核心A，行政 核心，将监督这两个项目的科学进展，促进项目之间的数据整合， 为中心提供管理责任和财务管理。核心B、基因表达和 Systems Immunology Core将负责RNA-seq、流式细胞术和质谱的数据分析 细胞计数，还将与Core A一起进行数据管理。Benaroya研究所拥有最先进的 艺术设施和技术设备，建立技术支持和受试者招募的基础设施， 和学院环境，以支持研究的建议。

项目成果

Cross-reactive and mono-reactive SARS-CoV-2 CD4+ T cells in prepandemic and COVID-19 convalescent individuals.

• DOI: 10.1371/journal.ppat.1010203
• 发表时间: 2021-12
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Johansson AM;Malhotra U;Kim YG;Gomez R;Krist MP;Wald A;Koelle DM;Kwok WW
• 通讯作者: Kwok WW

Oral desensitization therapy for peanut allergy induces dynamic changes in peanut-specific immune responses.

• DOI: 10.1111/all.15276
• 发表时间: 2022-08
• 期刊: ALLERGY
• 影响因子: 12.4
• 作者: Bajzik, Veronique;DeBerg, Hannah A.;Garabatos, Nahir;Rust, Blake J.;Obrien, Kimberly K.;Nguyen, Quynh-Anh;O'Rourke, Colin;Smith, Alex;Walker, Alex H.;Quinn, Charlie;Gersuk, Vivian H.;Farrington, Mary;Jeong, David;Vickery, Brian P.;Adelman, Daniel C.;Wambre, Erik
• 通讯作者: Wambre, Erik