LJI Epitope Validation Center: Characterization of epitope-specific T cells responding to food, fungal and inner city allergens

LJI 表位验证中心：表征对食物、真菌和市中心过敏原做出反应的表位特异性 T 细胞

• 批准号: 10083696
• 负责人: Alessandro Sette
• 金额: $ 127.92万
• 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/10083696
• 关键词: Address; Adult; Allergen Immunotherapy; Allergens; Allergic; Allergic Disease; Alternaria; Antigens; Aspergillus; Asthma; Biological Assay; CD4 Positive T Lymphocytes; Cattle; Cells; Characteristics; Child; Childhood; Childhood Asthma; Clinical; Collaborations; Consumption; Development; Diagnostic; Dictyoptera; Disease; Epitopes; Evolution; Exposure to; Flow Cytometry; Food; Food Hypersensitivity; Food Protein-Induced Enterocolitis Syndrome; Funding; Gene Expression Profile; Genetic; German population; Goals; Household; Hypersensitivity; Immune response; Individual; Infant; Inhalation; Interleukin-17; Interleukin-5; Investigation; Measurement; Messenger RNA; Milk; Milk Hypersensitivity; Modality; Molecular; Molecular Profiling; Mus; National Institute of Allergy and Infectious Disease; Nose; Occupational Exposure; Oral; Patients; Phenotype; Production; Proteins; Sampling; Sampling Studies; Severities; Severity of illness; Source; Specificity; Specimen; Sputum; System; T cell receptor repertoire sequencing; T cell response; T-Lymphocyte; T-cell receptor repertoire; Targeted Research; Teenagers; Therapeutic; Time; Up-Regulation; Validation; Wood material; Work; antigen-specific T cells; asthmatic; base; clinical phenotype; clinical practice; cockroach allergen; cohort; comparative; cytokine; desensitization; enzyme linked immunospot assay; food allergen; high risk; improved; inner city; insight; longitudinal analysis; mouse allergen; novel diagnostics; novel therapeutic intervention; programs; prospective; response; single-cell RNA sequencing; synergism; transcriptome sequencing; urban setting

CENTER PROGRAM SUMMARY/ABSTRACT Our proposal will use epitopes to comparatively evaluate immune responses in three different prototypic allergic diseases. We will study cockroach (CR) and mouse (MO) inhalation allergens, which are associated with the development of asthma in inner city children (Project 1); cow’s milk (CM), the most prevalently recognized pediatric food allergen (Project 2); and Aspergillus (ASP) and Alternaria (ALT) fungal allergens, which are associated with severe forms of asthma (Project 3). The extensive scientific overlap will offer opportunities for synergies between projects. Our study extensively utilizes cohorts independently funded by NIAID, to further multiply synergies and impact of the investigations. The evolution of responses will be examined as a function of time following natural exposure, exposure as part of work-duties and allergen immunotherapy (AIT). We will also study and compare individuals that are exposed but remain healthy, to people that have mild allergies and those that have severe asthma. Our hypothesis is that these distinct groups can be distinguished on the basis of their T cell response. Specifically, different groups might recognize different protein allergens or fragments (epitopes). It is also possible that the protein and genetic programs characteristic of T cells (T cell phenotypes) seen in allergic diseases of different types and severity will be unique. Our additional hypotheses are that evolution of T cell phenotypes can give us insights into the mechanism of allergic and asthmatic disease. If this were to be the case, it would have potential diagnostic value, and possibly suggest new therapeutic interventions.

中心项目概要/摘要 我们的建议将使用表位来比较评估三种不同原型的免疫反应 我们将研究相关的蟑螂（CR）和小鼠（MO）吸入过敏原。 内城区儿童哮喘的发生（项目 1）； 公认的儿科食物过敏原（项目 2）；以及曲霉属 (ASP) 和链格孢属 (ALT) 真菌过敏原， 与严重的哮喘相关（项目 3）。 我们的研究主要利用由独立资助的群体。 NIAID，为了进一步扩大调查的协同作用和影响，应对措施的演变将是。 作为自然暴露、工作职责一部分的暴露和过敏原后时间的函数进行检查 我们还将研究和比较暴露于病毒但仍保持健康的个体。 患有轻度过敏的人和患有严重哮喘的人我们的假设是这些不同的群体。 可以根据 T 细胞反应来区分，具体来说，不同的群体可能会识别。 不同的蛋白质过敏原或片段（表位）也有可能是蛋白质和遗传程序。 不同类型和严重程度的过敏性疾病中所见的 T 细胞特征（T 细胞表型） 我们的额外假设是，T 细胞表型的进化可以让我们深入了解 T 细胞表型。 如果确实如此，它将具有潜在的诊断价值。 值，并可能建议新的治疗干预措施。