The rat as new model for the analysis of iNKT cell antigen-recognition and function

大鼠作为 iNKT 细胞抗原识别和功能分析的新模型

• 批准号: 207628071
• 负责人: Professor Dr. Thomas Herrmann
• 金额: --
• 依托单位: Institut für Virologie und Immunbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/207628071?language=en
• 关键词: rat; new; model; analysis; iNKT

iNKT cells, also designated as type I NKT cells, fight against pathogens and tumors, and suppress autoimmune diseases but they can also promote development of numerous pathological conditions. Their hallmark is the expression of a characteristic type of T-cell antigen receptor (iNKT-TCR), which recognizes complexes of (glyco)lipids and the cell surface molecule CD1d. All iNKT-TCRs contain an invariant α-chain, whose antigen-binding site is encoded by the TCR-AV14 gene and the -AJ18 gene. New tools developed by our group will allow for the first time direct analysis of iNKT cells in the rat. The first part aims for a better understanding of the mechanisms of antigen-recognition by iNKT-TCRs. To this end iNKT-TCR mutants and TCRs from iNKT cell subpopulations will be analyzed for antigenbinding and specifically to which extent rat AV14 gene-variability may affect antigen-recognition. The second part of the project uses similarities between rat and human iNKT cells to establish the rat as new model for therapeutic applications of iNKT cells. iNKT cells will be expanded in vitro and selected for desired features such as production of certain cytokines. Subsequently, these iNKT cells will be transferred into immunocompetent or irradiated animals and fate and function of the iNKT cells will be studied.

iNKT细胞，也称为I型NKT细胞，对抗病原体和肿瘤，并抑制自身免疫性疾病，但它们也可以促进许多病理状况的发展。它们的标志是一种特征性类型的T细胞抗原受体（iNKT-TCR）的表达，该受体识别（糖）脂质和细胞表面分子CD 1d的复合物。所有iNKT-TCR都含有一个不变的α链，其抗原结合位点由TCR-AV 14基因和-AJ18基因编码。我们团队开发的新工具将首次允许直接分析大鼠中的iNKT细胞。第一部分旨在更好地理解iNKT-TCR的抗原识别机制。为此，将分析iNKT细胞亚群的iNKT-TCR突变体和TCR的抗原结合，特别是大鼠AV 14基因变异性可能影响抗原识别的程度。该项目的第二部分利用大鼠和人类iNKT细胞之间的相似性，将大鼠建立为iNKT细胞治疗应用的新模型。iNKT细胞将在体外扩增并针对所需特征（例如某些细胞因子的产生）进行选择。随后，将这些iNKT细胞转移到免疫活性或辐照动物中，并研究iNKT细胞的命运和功能。