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: 10321623
• 负责人: Alessandro Sette
• 金额: $ 35.28万
• 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/10321623
• 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 我们的建议集中在蟑螂（CR）和老鼠（MO）过敏原，主要在内城儿童 与日后过敏性哮喘的发生有关。我们还依赖其他抗原表位 过敏原和破伤风类毒素（TT）和百日咳（PT）抗原，作为重要的特异性对照。我们 研究将回答RFA的问题：“具有特定表位的T细胞的存在是否 特异性区分过敏和非过敏个体？”我们已经发现了大量的 差异，在CR和MO系统，支持的理由和可行性， 工作我们将确定在非过敏性和过敏性与不同疾病的反应表位 严重性我们计划接下来回答这些问题：“在过敏症患者中，特异性T细胞表位 区分不同的临床表型或疾病严重程度的阶段？有多重要 表位特异性T细胞的免疫表型作为临床表现的标志物？我们将研究 从哮喘发展高风险家庭的儿童中采集样本。我们将 计数过敏原特异性T细胞的数量，并确定其蛋白质表达模式， 基因图谱最后，我们会问：“随着时间的推移，表位特异性T细胞库有多稳定， 在个体中，基因库的自然改变有什么临床意义？并 过敏原暴露或AIT会影响一组特定的表位特异性T细胞吗？”样本 不同的供体组将根据过敏原特异性T细胞、蛋白质和免疫原性T细胞的数量来表征。 基因图谱我们将研究来自CoNAC（蟑螂鼻变应原挑战）研究的样本， 由ICAC网络在敏感和非敏感捐赠者中进行。我们亦会研究 来自内部建立的MO非致敏供体队列的纵向样本， 由于职业原因，严重暴露于MO过敏原。最后，我们将研究纵向 来自免疫治疗临床试验的样品，包括用CR提取物或安慰剂治疗的个体。 我们将测量对CR过敏原的反应的演变。此外，我们还将评估 对供体致敏或非致敏的其他过敏原，以确定是否 免疫疗法仅调节CR应答，或者还调节对其它过敏原特异的T细胞。