TCR USAGE AND FUNCTION IN IBD

描述(取自应用程序) T细胞可能在炎症性肠病中发挥关键作用。 (IBD)发病机制。我们的重点是对T细胞的分析 受体(TCR)，T细胞的特异性抗原识别元件，作为一种 T细胞对特定抗原(S)反应在疾病中的作用 发病机制和潜在的识别疾病相关的T细胞克隆。 我们之前对TCR使用情况的研究清楚地表明，高度特异的 IBD患者存在T细胞反应，这种反应是 以持续的T细胞扩张为特征的，这与 基因相关的个体。这直接暗示了 炎症性肠病患者中的T细胞对常规抗原有影响(S)。少校 这项拨款提案的目标是进一步定义这些项目的性质 炎性肠病患者T细胞的扩增及其潜在识别T细胞的研究 与IBD发病相关的抗原(S)。具体地说，我们计划 特征：(1)IL-2受体阳性亚群的TCR使用率 肠道T细胞；(2)胆管相关T细胞的TCR使用率 临床上不同的原发性硬化症患者亚群 胆管炎；(3)主要组织相容性的关系 炎症性肠病家族中的复合体(MHC)和TCR的使用。通过利用这一点 有关TCR使用情况的信息，特定的感兴趣T细胞克隆，其表达 属于公共或私人主题的TCR将被隔离并 在长期、分子和基于细胞的战略中使用。这些 以快速新兴技术为基础的战略将致力于 确定这些潜在疾病相关T细胞的同源抗原(S)， 从而进一步了解IBD的病因。

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.