TCR USAGE AND FUNCTION IN IBD

TCR 在 IBD 中的用途和功能

• 批准号: 6380061
• 负责人: LAWRENCE J SAUBERMANN
• 金额: $ 11.94万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380061
• 关键词: Epstein Barr virus; MHC class I antigen; T cell receptor; antigen presentation; biliary tract disorder; cell line; complementary DNA; cytokine receptors; disease /disorder etiology; family genetics; flow cytometry; genetic library; inflammation; inflammatory bowel diseases; interleukin 2; lymphocyte proliferation; major histocompatibility complex; polymerase chain reaction

DESCRIPTION (taken from application) T-cells are likely to play a crucial role in inflammatory bowel disease (IBD) pathogenesis. Our focus has centered on the analysis of the T-cell receptor (TCR), the specific antigen recognition element of the T-cell, as a means to implicate T-cell responses to specific antigen(s) in disease pathogenesis and to potentially identify disease relevant T-cell clones. Our previous studies on TCR usage have clearly shown that a highly specific T-cell response is present in individuals with IBD and this response is characterized by persistent T-cell expansions which are shared by genetically related individuals. This directly implicates a response by T-cells in IBD affected individuals to conventional antigen(s). The major goals of this grant proposal are to further define the nature of these T-cell expansions in IBD and investigate for potential T-cell recognized antigen(s) relevant to IBD pathogenesis. Specifically, we plan to characterize: (1) the TCR usage of the IL-2 receptor positive subset of intestinal T-cells; (2) the TCR usage of the bile-duct associated T-cells in the clinically distinct subset of individuals with primary sclerosing cholangitis, and; (3) the relationship between major histocompatibility complex (MHC) and TCR usage in families with IBD. By utilizing this information on TCR usage, specific T-cell clones of interest, which express TCRs that are a part of a public or private motif, will be isolated and utilized in long-term, molecular and cellular based strategies. These strategies, which are based on rapidly emerging technologies, will aim to define the cognate antigen(s) of these potentially disease relevant T-cells, and thus allow further insight into the etiopathogenesis of IBD.

描述（取自申请） T 细胞可能在炎症性肠病中发挥关键作用 （炎症性肠病）发病机制。 我们的重点是 T 细胞的分析 受体（TCR），T细胞的特异性抗原识别元件，作为 表示 T 细胞对疾病中特定抗原的反应 发病机制并有可能识别疾病相关的 T 细胞克隆。 我们之前对 TCR 使用的研究清楚地表明，高度特异性的 T 细胞反应存在于 IBD 个体中，并且这种反应是 其特征是持续的 T 细胞扩增，其共享 具有遗传相关性的个体。 这直接暗示了响应 IBD 中的 T 细胞影响个体对传统抗原的抵抗力。 主要 该赠款提案的目标是进一步界定这些项目的性质 IBD 中的 T 细胞扩增并研究潜在的 T 细胞识别 与 IBD 发病机制相关的抗原。 具体来说，我们计划 表征：（1）IL-2受体阳性子集的TCR用途 肠道 T 细胞； (2)胆管相关T细胞的TCR用途 患有原发性硬化症的临床上不同的个体子集 胆管炎； (3)主要组织相容性的关系 IBD 家族中复合体 (MHC) 和 TCR 的使用。 通过利用这个 有关 TCR 使用、感兴趣的特定 T 细胞克隆的信息，这些克隆表达 作为公共或私人主题一部分的 TCR 将被隔离并 用于长期、分子和细胞策略。 这些 基于快速新兴技术的战略将旨在 定义这些潜在疾病相关 T 细胞的同源抗原， 从而进一步了解 IBD 的发病机制。