Understanding mechanisms in specific immunotherapy (SIT)

了解特异性免疫疗法 (SIT) 的机制

• 批准号: 8442252
• 负责人: Bjoern Peters
• 金额: $ 24.53万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8442252
• 关键词: Allergens; Allergic; Allergic Disease; Allergy Shot; Antibodies; Antibody Formation; Antigens; Biological Markers; Cells; Data; Epitopes; Gel; Gene Expression Profile; Hypersensitivity; IgE; Immune response; Immunoblotting; Immunoglobulin G; Immunotherapy; Individual; Instruction; Knowledge; Longitudinal Studies; Monitor; Outcome; Peripheral Blood Mononuclear Cell; Phenotype; Phleum; Play; Production; Proteome; Role; Safety; Specificity; System; T cell response; T-Lymphocyte; Testing; Validation; Work; base; grass pollen; novel; prevent; response

PROJECT SUMMARY (See instructions): SIT is widely accepted as a useful treatment of allergic disease despite an incomplete knowledge of mechanism of action and variability in efficacy. This project is focused on understanding mechanisms behind SIT and specifically tests the hypothesis that certain allergens, antigens, and epitopes are more prominently or potentially differentially recognized by SIT treated donors as compared to untreated allergic individuals. We further test the related hypothesis that responses to certain novel anfigens, recently identified by our group, may play a role in the successful outcome of SIT treatment. By characterizing the functional phenotype ofthe T cell responses to the known and novel antigens alike, we will identify changes occurring as a result of SIT. We will also test two specific hypotheses on mechanisms associated with SIT, namely: 1) SIT modulates Tfh cells to promote a shift from IgE to IgG production and that 2) SIT induces Tri cells with suppressive regulatory capacity. Previous work from our group in the Timothy grass (TG) system delineated the major epitopes associated with ten known major allergens in allergic and SIT treated donors. In those major TG allergens, we did not identify major targets of ILIO producing T cells. Recent data from our group using a transcriptome and proteome analysis of TG pollen and 2D gel immunoblots with IgE and IgG antibodies from SIT and allergic donors has led to the identification of several novel antigens that are selectively recognized by antibodies from SIT individuals, induce IgG (but not IgE) responses, and others that do not induce an antibody response. Several of these novel antigens are vigorously recognized by T cells, particularly from PBMC from SIT donors. Our studies will test the hypothesis that qualitative shifts in response specificity may be important in inducing efficacy of SIT. Epitopes from both known and novel antigens will be used in longitudinal studies, monitoring magnitude and phenotype of responding T cells. If successful, the proposed studies will highlight potentially useful novel immunogens for use in place of current SIT that may be safer and more effective. In addition, our studies may identify biomarkers that indicate successful SIT treatment.

项目摘要（请参阅说明）： 尽管不完整了解 作用机理和疗效的可变性。该项目的重点是理解背后的机制 坐着并特别检验了某些过敏原，抗原和表位的假设更为突出 与未经治疗的过敏个体相比，或者由SIT治疗的捐助者识别出潜在的差异性识别。 我们进一步检验了相关的假设，即对某些新型生物生物的反应，最近由我们的 小组可能在SIT治疗的成功结果中发挥作用。通过表征功能 T细胞对已知和新型抗原的反应的表型，我们将确定发生的变化 由于SIT。我们还将检验有关与SIT相关的机制的两个特定假设，即：1） SIT调节TFH细胞以促进从IgE到IgG产生的转变，并且2）SIT诱导Tri细胞与 抑制监管能力。我们小组的蒂莫西草（TG）系统的先前工作已划定 与在过敏性和现场治疗的供体中相关的十个已知主要过敏原相关的主要表位。在那些 主要TG过敏原，我们没有确定产生T细胞的ILIO的主要靶标。我们小组的最新数据 使用带有IgE和IgG的TG花粉和2D凝胶免疫印迹的转录组和蛋白质组分析 SIT和过敏供体的抗体导致了几种新型抗原的鉴定 通过SIT个体的抗体有选择地识别，诱导IgG（但不是IgE）的反应，而其他反应 不会诱导抗体反应。这些新型抗原中的几种被T剧烈识别 细胞，特别是来自现场供体的PBMC。我们的研究将检验以下假设 响应特异性对于诱导SIT功效很重要。来自已知和新颖的表位 抗原将用于纵向研究，监测响应T细胞的幅度和表型。如果 成功的研究将突出显示潜在有用的新型免疫原，以代替当前 坐下可能更安全，更有效。此外，我们的研究可能确定表明的生物标志物 成功的SIT治疗。