Listeria Epitopes TCR Transgenics Antigen Sensitivity and Early Signaling

在过去30年左右的时间里，对T细胞对“模型”抗原的反应进行了密集的研究，取得了许多成果 对T细胞生物学和功能的洞察力，特别是与识别特定多肽-MHC有关的 复合体通过T细胞受体寻找抗原。 与这个项目特别相关的是，现在有很好的证据表明，成熟的T细胞对 即使是激动剂(肽-MHC)配体的单个分子，这种非凡的敏感性至少在 DART是通过特定的内源性多肽-MHC复合体与 触发TCR二聚化的激动剂。我们现在希望将这些研究扩展到对CD4和CDS的分析 李斯特菌不同时期、不同发育阶段的T细胞反应性 小鼠的单核细胞增多性感染。 我们特别希望验证这样一种假设，即在李斯特菌感染期间出现的占主导地位的T细胞 因此，因为它们具有优越的信号特性。 这些研究将涉及制作一系列针对李斯特菌LLO表位和 检测这些转基因细胞的敏感性和自始至终具有保护性的能力。这个项目将涉及 高量化的实验数据与最先进的建模技术之间的紧密接口。

In the past 30 years or so, intensive work on T cell responses to 'model' antigens has resulted in a great deal of insight into T cell biology and function, particularly as it relates to the recognition of specific peptide-MHC complexes through the T cell receptor for antigen. Of particular relevance to this project, there is now good evidence that mature T cell blasts are sensitive to even a single molecule of an agonist (peptide-MHC) ligand and that this extraordinary sensitivity is at least in Dart achieved by the engagement of particular endogenous peptide-MHC complexes together with the agonist in triggering TCR dimerization. We now wish to extend these studies to the analysis of CD4 and CDS T cell responsiveness as different times and with different developmental stages of T cells during Listeria monocytogenes infection in mice. We particularly wish to test the hypothesis that T cells which emerge as dominant during Listeria infection do so because they have superior signaling properties. These studies will involve making a series of CD4transgenics specific for a Listeria LLO epitope and assaying these transgenic cells for sensitivity and ability to be protective throughout. This project will involve the close interfacing between highly quantitative experimental data and state of the art modeling techniques.