Listeria Epitopes TCR Transgenics Antigen Sensitivity and Early Signaling

李斯特菌表位 TCR 转基因抗原敏感性和早期信号传导

• 批准号: 8098135
• 负责人: Mark Morris Davis
• 金额: $ 35.88万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 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/8098135
• 关键词: Agonist; Antigens; Arts; Avidity; Biochemistry; Biological Assay; Biological Models; Blast Cell; CD4 Positive T Lymphocytes; Calcium; Cells; Cellular Immunity; Cellular Immunology; Cellular biology; Data; Development; Dimerization; Epitopes; Event; Goals; Histocompatibility Antigens Class II; Image; Immune response; Immunity; Immunocompromised Host; In Vitro; Infection; Interferons; Interleukin-2; Laboratories; Ligands; Listeria; Listeria monocytogenes; Listeriosis; MHC Class I Genes; MHC Class II Genes; Macrophage Activation; Mature T-Lymphocyte; Memory; Modeling; Molecular; Mus; Natural Killer Cells; Ovalbumin; Ovum; Peptide/MHC Complex; Peptides; Play; Production; Proliferating; Property; Reagent; Research Personnel; Role; Sensitivity and Specificity; Series; Signal Transduction; Staging; T cell response; T memory cell; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Techniques; Testing; Time; Transgenic Mice; Transgenic Organisms; Virulence; Work; computer studies; experience; insight; interest; killings; membrane model; pathogen; programs; research study; response; single molecule; synaptogenesis

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.

在过去 30 年左右的时间里，T 细胞对“模型”抗原反应的深入研究已经取得了很多成果。 深入了解 T 细胞生物学和功能，特别是与特定肽-MHC 的识别相关 通过T细胞抗原受体形成复合物。 与该项目特别相关的是，现在有充分的证据表明成熟的 T 细胞母细胞对 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 通过特定的内源性肽-MHC 复合物与 触发 TCR 二聚化的激动剂。我们现在希望将这些研究扩展到 CD4 和 CDS 的分析 李斯特菌感染期间不同时间和不同发育阶段的 T 细胞反应 小鼠单核细胞增多症感染。 我们特别希望检验以下假设：在李斯特菌感染期间占主导地位的 T 细胞确实 因为它们具有卓越的信号特性。 这些研究将涉及制作一系列针对李斯特菌 LLO 表位的 CD4 转基因技术 检测这些转基因细胞的敏感性和自始至终保护的能力。该项目将涉及 高度定量的实验数据和最先进的建模技术之间的紧密结合。