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: 10321619
• 负责人: Alessandro Sette
• 金额: $ 115.36万
• 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/10321619
• 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; Persons; 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; diagnostic value; 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.

中心计划摘要/摘要 我们的建议将使用表位来评估三种不同原型的免疫复杂 过敏性疾病。我们将研究蟑螂（CR）和小鼠（MO）吸入过敏原，它们与之相关 随着内城儿童哮喘的发展（项目1）；牛奶（CM），最普遍 公认的儿科过敏原（项目2）；和曲曲霉（ASP）和替代（Alt）真菌过敏原， 与严重的哮喘形式有关（项目3）。广泛的科学重叠将提供 项目之间协同作用的机会。我们的研究广泛地利用了由 NIAID，以进一步增加研究的协同作用和影响。回应的演变将是 自然暴露后的时间检查，作为工作任务的一部分和过敏原检查 免疫疗法（AIT）。我们还将研究和比较暴露但保持健康的个人 患有轻度过敏的人，患有严重哮喘的人。我们的假设是这些不同的群体 可以根据其T细胞反应来区分。具体而言，不同的群体可能会识别 不同的蛋白质过敏原或片段（表位）。蛋白质和遗传程序也可能 在不同类型和严重程度的过敏性疾病中看到的T细胞（T细胞表型）的特征将是 独特的。我们的其他假设是，T细胞表型的进化可以使我们深入了解 过敏和哮喘疾病的机制。如果是这种情况，它将具有潜在的诊断 价值，并可能提出新的治疗干预措施。

项目成果

Allergen content in German cockroach extracts and sensitization profiles to a new expanded set of cockroach allergens determine in vitro extract potency for IgE reactivity.

• DOI: 10.1016/j.jaci.2018.07.036
• 发表时间: 2019-04
• 期刊: The Journal of allergy and clinical immunology
• 作者: Glesner J;Filep S;Vailes LD;Wünschmann S;Chapman MD;Birrueta G;Frazier A;Jeong KY;Schal C;Bacharier L;Beigelman A;Busse P;Schulten V;Sette A;Pomés A
• 通讯作者: Pomés A

Urinary Peptides As a Novel Source of T Cell Allergen Epitopes.

• DOI: 10.3389/fimmu.2018.00886
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: da Silva Antunes R;Pham J;McMurtrey C;Hildebrand WH;Phillips E;Mallal S;Sidney J;Busse P;Peters B;Schulten V;Sette A
• 通讯作者: Sette A

Allergen and Epitope Targets of Mouse-Specific T Cell Responses in Allergy and Asthma.

过敏和哮喘中小鼠特异性 T 细胞反应的过敏原和表位靶标。

• DOI: 10.3389/fimmu.2018.00235
• 发表时间: 2018
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Schulten,Véronique;Westernberg,Luise;Birrueta,Giovanni;Sidney,John;Paul,Sinu;Busse,Paula;Peters,Bjoern;Sette,Alessandro
• 通讯作者: Sette,Alessandro

The association of allergic sensitization patterns in early childhood with disease manifestations and immunological reactivity at 10 years of age.

儿童早期过敏致敏模式与 10 岁时疾病表现和免疫反应性的关联。

• DOI: 10.1111/cea.13406
• 发表时间: 2019
• 期刊: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
• 作者: Schulten,Véronique;Frazier,April;Calatroni,Agustin;Kattan,Meyer;Bacharier,LeonardB;O'Connor,GeorgeT;Sandel,MeganT;Wood,RobertA;Wheatley,LisaM;Togias,Alkis;Visness,CynthiaM;Dresen,Amy;Gern,JamesE;Sette,Alessandro
• 通讯作者: Sette,Alessandro

Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors.

• DOI: 10.1016/j.crmeth.2022.100350
• 发表时间: 2022-12-19
• 期刊: Cell reports methods