IMMUNOLOGIC GLYCOSPHINGOLIPIDOMICS AND NKT CELL DEVELOPMENT IN MOUSE THYMUS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 恒定NKT细胞是自然杀伤细胞和T细胞的杂交细胞类型，其发育依赖于双阳性胸腺细胞介导的胸腺正选择，其通过识别由非多态性、非MHC、MHC样抗原呈递分子CD 1d呈递的天然配体。遗传证据表明，β-葡糖神经酰胺衍生的鞘糖脂（GSL）是NKT细胞的天然配体。N-丁基脱氧半乳糖野尻霉素（NB-DGJ）是一种特异性抑制葡萄糖神经酰胺合酶的药物，可抑制NKT细胞的内源性配体。此外，我们和其他人已经发现β-连接的鞘糖脂，isoglobotriaosylceramide（iGb 3），是一种刺激性NKT配体。iGb 3合酶敲除小鼠具有正常的NKT发育和功能，表明存在其他配体，并且仍有待鉴定。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting molecule. Genetic evidence suggested that beta-glucosylceramide derived glycosphingolipids (GSLs) are natural ligands for NKT cells. N-butyldeoxygalactonojirimycin (NB-DGJ), a drug that specifically inhibits the glucosylceramide synthase, inhibits the endogenous ligands for NKT cells. Furthermore, we and others have found a beta-linked glycosphingolipid, isoglobotriaosylceramide (iGb3), is a stimulatory NKT ligand. The iGb3 synthase knockout mice have a normal NKT development and function, indicating that other ligands exist and remain to be identified.