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

项目总结 我们的建议侧重于蟑螂(CR)和老鼠(MO)过敏原，这两种过敏原主要存在于市中心的儿童中 与晚年过敏性哮喘的发展有关。我们还依赖于其他生物的表位 变应原、破伤风类毒素(TT)和百日咳(PT)抗原作为重要的特异性对照。我们的 研究将回答RFA的问题：具有特定表位的T细胞的存在 过敏的人和不过敏的人有什么不同？“我们已经发现了重要的 CR和MO系统的差异，支持拟议的理由和可行性 工作。我们将在非过敏症和不同疾病的过敏症中定义具有反应性的表位 严肃性。我们计划下一步回答这些问题：在过敏患者中，做特定的T细胞表位 区分疾病严重程度的不同临床表型或阶段？这件事有多重要 表位特异性T细胞的免疫学表型是临床表现的标志吗？我们会研究 随着时间的推移，从哮喘高危家庭的儿童身上采集样本。我们会 计算过敏原特异性T细胞的数量，并确定它们的蛋白表达模式和 基因图谱。最后，我们会问：“随着时间和时间的推移，表位特异性T细胞谱系的稳定性如何？ 个体体内谱系的自然改变有哪些临床意义？会吗？ 过敏原暴露或AIT会影响一组特定的表位特异性T细胞吗？样品来自 不同的捐赠者队列将根据过敏原特异性T细胞、蛋白质和 基因图谱。我们将研究CONAC(蟑螂鼻过敏原挑战)研究的样本， 由廉政公署网络对敏感和非敏感捐赠者实施。我们还将检查 来自内部建立的捐赠者队列的纵向样本是MO非致敏的，但， 因职业原因，严重接触MO过敏原。最后，我们将进行纵向研究。 来自免疫治疗临床试验的样本，包括接受CR提取物或安慰剂治疗的个体。 我们将测量对CR变应原的反应的演变。此外，我们还将衡量人们的反应 对捐赠者致敏或非致敏的其他过敏原，以确定 免疫疗法只调节CR反应，或者也调节针对其他过敏原的T细胞。

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.