Kinjo Yuki, Pei Bo, Bufali Simone, Raju Ravinder, Richardson Stewart K, Imamura Masakazu, Fujio Masakazu, Wu Douglass, Khurana Archana, Kawahara Kazuyoshi, Wong Chi-Huey, Howell Amy R, Seeberger Peter H, Kronenberg Mitchell
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Chem Biol. 2008 Jul 21;15(7):654-64. doi: 10.1016/j.chembiol.2008.05.012.
Mouse natural killer T (NKT) cells expressing an invariant T cell antigen receptor (TCR) recognize glycosphingolipids (GSLs) from Sphingomonas bacteria. The synthetic antigens previously tested, however, were designed to closely resemble the potent synthetic agonist alpha-galactosyl ceramide (alphaGalCer), which contains a monosaccharide and a C18:0 sphingosine lipid. Some Sphingomonas bacteria, however, also have oligosaccharide-containing GSLs, and they normally synthesize several GSLs with different sphingosine chains including one with a cyclopropyl ring-containing C21:0 (C21cycl) sphingosine. Here we studied the stimulation of NKT cells with synthetic GSL antigens containing natural tetrasaccharide sugars, or the C21cycl sphingosine. Our results indicate that there is a great degree of variability in the antigenic potency of different natural Sphingomonas glycolipids, with the C21cycl sphingosine having intermediate potency and the oligosaccharide-containing antigens exhibiting limited or no stimulatory capacity.
表达恒定T细胞抗原受体(TCR)的小鼠自然杀伤T(NKT)细胞可识别来自鞘氨醇单胞菌属细菌的糖鞘脂(GSL)。然而,之前测试的合成抗原旨在与强效合成激动剂α-半乳糖基神经酰胺(αGalCer)高度相似,αGalCer含有一个单糖和一条C18:0鞘氨醇脂质链。然而,一些鞘氨醇单胞菌属细菌也含有含寡糖的GSL,并且它们通常会合成几种具有不同鞘氨醇链的GSL,其中一种含有含环丙基的C21:0(C21cycl)鞘氨醇。在此,我们研究了含有天然四糖或C21cycl鞘氨醇的合成GSL抗原对NKT细胞的刺激作用。我们的结果表明,不同天然鞘氨醇单胞菌糖脂的抗原效力存在很大差异,C21cycl鞘氨醇具有中等效力,而含寡糖的抗原表现出有限的或无刺激能力。