Cockroach and mouse allergy T cell phenotypes and their correlation with clinical status

蟑螂和小鼠过敏 T 细胞表型及其与临床状态的相关性

• 批准号: 10083709
• 负责人: Alessandro Sette
• 金额: $ 41.82万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10083709
• 关键词: 10 year old; 13 year old; Address; Adult; Allergen Immunotherapy; Allergens; Allergic; Allergic Disease; Antigens; Asthma; Biological Assay; Blood; Cell surface; Cells; Cellular Assay; Child; Childhood; Childhood Asthma; Clinical; Data; Development; Dictyoptera; Disease Outcome; Epitope Mapping; Epitopes; Evolution; Exposure to; Extrinsic asthma; Food; Funding; Genetic; Household; Hypersensitivity; Immune; Immune response; Immunologics; Immunophenotyping; Immunotherapy; Individual; Interferon Type II; Interleukin-10; Interleukin-17; Interleukin-5; Investigation; Life; Longitudinal Studies; Measures; Messenger RNA; Monitor; Mus; Nature; Nose; Occupational; Occupations; Pattern; Peptides; Peripheral Blood Mononuclear Cell; Persons; Pertussis; Phenotype; Placebos; Production; Proteins; Proteomics; Sampling; Sampling Studies; Severity of illness; Specificity; System; T cell response; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Epitopes; T-Lymphocyte Subsets; T-cell receptor repertoire; Tetanus Toxoid; Time; Translating; Validation; Work; clinical phenotype; cockroach allergen; cohort; cytokine; enzyme linked immunospot assay; high risk; immunotherapy clinical trials; immunotherapy trials; inner city; mouse allergen; mouse allergy; novel; protein expression; response; synergism; transcriptome sequencing; urban setting

PROJECT SUMMARY Our proposal focuses on cockroach (CR) and mouse (MO) allergens, dominant in inner city children correlated with development of allergic asthma later on in life. We also rely on epitopes from other allergens and tetanus toxoid (TT) and pertussis (PT) antigens, as important specificity controls. Our studies will answer the RFA question: “Does the presence of T-cells with particular epitope specificities differentiate allergic from non-allergic individuals?” We have already detected significant differences, in both the CR and MO systems, supporting the rationale and feasibility of the proposed work. We will define epitopes with reactivity in non-allergics and allergics with different disease severities. We plan to next answer the questions; “In persons with allergy, do specific T-cell epitopes differentiate between various clinical phenotypes or stages of disease severity? How important is the immunologic phenotype of epitope-specific T-cells as a marker of clinical presentation?” We will study samples taken over time from children from households at high-risk for asthma development. We will count the number of allergen-specific T cells, and define their pattern of protein expression and genetic profiles. Finally, we will ask: “How stable is the epitope-specific T-cell repertoire over time and what are the clinical implications of natural alterations in the repertoire within individuals? Does allergen exposure or AIT influence a particular group of epitope-specific T-cells?” Samples from various donor cohorts will be characterized in terms of number of allergen-specific T cells, protein and genetic profiles. We will study samples from the CoNAC (Cockroach Nasal Allergen Challenge) study, performed by the ICAC network, in sensitized and non-sensitized donors. We will also examine longitudinal samples from an in-house established cohort of donors that are MO non-sensitized but, because of occupational duties, heavily exposed to MO allergens. Finally, we will study longitudinal samples from immunotherapy clinical trials including individuals treated with CR extract or placebo. We will measure the evolution of responses to CR allergens. In addition, we will measure responses to other allergens to which donors are either sensitized or non-sensitized to establish whether immunotherapy only modulates CR responses, or also modulates T cells specific for other allergens.

项目摘要 我们的建议重点是蟑螂（CR）和鼠标（MO）过敏原，在内城儿童中占主导地位 与后来生活中的过敏性哮喘的发展有关。我们还依靠其他的表位 过敏原和破伤风毒素（TT）和百日咳（PT）抗原，作为重要的特异性控制。我们的 研究将回答RFA问题：“与特定表位的T细胞的存在是否存在 特异性将过敏与非过敏性个体区分开吗？”我们已经检测到了重要的 在CR和MO​​系统中的差异，支持所提出的理由和可行性 工作。我们将定义具有不同疾病的非过敏和过敏性反应性的表位 严重性。我们计划下一步回答问题； “对过敏的人，做特定的T细胞表位 区分各种临床表型或疾病严重程度的阶段？有多重要 表位特异性T细胞作为临床表现标志的免疫学表型？”我们将研究 随着时间的流逝，来自高危家庭的儿童进行哮喘发育的样本。我们将 计算过敏原特异性T细胞的数量，并定义其蛋白质表达模式和 遗传特征。最后，我们会问：“随着时间的流逝，表位特异性T细胞曲目的稳定性如何 个人内部曲目自然改变的临床意义是什么？做 过敏原暴露或AIT影响特定表位特异性T细胞？ 各种供体队列将以过敏原特异性T细胞，蛋白质和 遗传特征。我们将研究CONAC（蟑螂鼻过敏素挑战）的样品， 由ICAC网络，敏感和非敏感供体进行。我们还将检查 来自内部的纵向样本建立了一群不敏感的捐助者，但 由于占用职责，大量暴露于MO过敏原。最后，我们将学习纵向 来自免疫疗法临床试验的样本，包括接受CR提取物或安慰剂治疗的个体。 我们将衡量对CR过敏原反应的演变。此外，我们将衡量答复 对于供体敏感或不敏感的其他过敏原来确定是否是 免疫疗法仅调节CR反应，或者调节针对其他过敏原特异性的T细胞。