Sriram Venkataraman, Du Wenjun, Gervay-Hague Jacquelyn, Brutkiewicz Randy R
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202-5254, USA.
Eur J Immunol. 2005 Jun;35(6):1692-701. doi: 10.1002/eji.200526157.
The current consensus on characterization of NKT cells is based on their reactivity to the synthetic glycolipid, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Because of the limited availability of alpha-GalCer, there is a constant search for CD1d-presented ligands that activate NKT cells. The alpha-anomericity of the carbohydrate is considered to be an important requisite for the CD1d-specific activation of NKT cells. The gram-negative, lipopolysaccharide-free bacterium Sphingomonas paucimobilis is known to contain glycosphingolipids (GSL) with alpha-anomeric sugars attached to the lipid chain. Here, we report that GSL extracted from this bacterium are able to stimulate NKT cells in a CD1d-specific manner. In addition, soluble CD1d-Ig dimers loaded with this lipid extract specifically bind to NKT cells (but not conventional T cells). Further studies on the S. paucimobilis GSL could potentially lead to other natural sources of CD1d-specific ligands useful for NKT cell analyses and aimed at identifying novel therapies for a variety of disease states.
目前关于自然杀伤T细胞(NKT细胞)特征的共识是基于它们以CD1d依赖的方式对合成糖脂α-半乳糖神经酰胺(α-GalCer)的反应性。由于α-GalCer的可用性有限,人们一直在不断寻找能激活NKT细胞的由CD1d呈递的配体。碳水化合物的α异头物被认为是NKT细胞CD1d特异性激活的重要必要条件。已知革兰氏阴性、无脂多糖的少动鞘氨醇单胞菌含有糖鞘脂(GSL),其脂质链上连接有α异头糖。在此,我们报告从这种细菌中提取的GSL能够以CD1d特异性的方式刺激NKT细胞。此外,负载有这种脂质提取物的可溶性CD1d-Ig二聚体特异性结合NKT细胞(而非传统T细胞)。对少动鞘氨醇单胞菌GSL的进一步研究可能会找到其他天然来源的CD1d特异性配体,这些配体可用于NKT细胞分析,并旨在确定针对多种疾病状态的新疗法。