Synthetic α-mannosyl ceramide as a potent stimulant for an NKT cell repertoire bearing the invariant Vα19-Jα26 TCR α chain
Synthetic α-mannosyl ceramide as a potent stimulant for an NKT cell repertoire bearing the invariant Vα19-Jα26 TCR α chain
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DOI：
10.1016/j.chembiol.2005.04.014
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发表时间：
2005-06-01
影响因子：
--
通讯作者：
Shimamura, M
中科院分区：
文献类型：
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作者：
Okamoto, N;Kanie, O;Shimamura, M
NKT细胞库的特征是表达V α 19- j α 26不变的TCR α链（V α 19 NKT细胞）。这一基因库，以及一个完善的V α 14- j α 281不变的TCR α NKT细胞亚群（V α 14 NKT细胞），已被认为在免疫系统调节中具有重要作用，因此是一个主要的治疗靶点。在这里，我们试图找到V α 19 NKT细胞的特异性抗原。V α 19和V α 14 NKT细胞对α -半乳糖神经酰胺（α - galcer）表现出反应性。因此，我们合成了一系列在糖和神经酰胺部分之间具有轴向糖苷键的单糖基神经酰胺，并通过测量它们在糖脂培养中的免疫反应来确定它们对V α 19 NKT细胞的抗原性。综合检查显示，α -甘露糖基神经酰胺对V α 19 NKT细胞具有显著的抗原活性。
A NKT cell repertoire is characterized by the expression of the V alpha 19-J alpha 26 invariant TCR alpha chain (V alpha 19 NKT cell). This repertoire, as well as a well-established V alpha 14-J alpha 281 invariant TCR alpha NKT cell subset (V alpha 14 NKT cell), has been suggested to have important roles in the regulation of the immune system and, thus, is a major therapeutic target. Here, we attempted to find specific antigens for V alpha 19 NKT cells. V alpha 19 as well as V alpha 14 NKT cells exhibited reactivity to a.-galactosyl ceramide (alpha-GalCer). Thus, a series of monoglycosyl ceramides with an axially oriented glycosidic linkage between the sugar and ceramide moiety were synthesized and their antigenicity to V alpha 19 NKT cells was determined by measuring their immune responses in culture with glycolipids. Comprehensive examinations revealed substantial antigenic activity for V alpha 19 NKT cells by alpha-mannosyl ceramide.