Mycolic Acids Constitute a Scaffold for Mycobacterial Lipid Antigens Stimulating CD1-Restricted T Cells
Mycolic Acids Constitute a Scaffold for Mycobacterial Lipid Antigens Stimulating CD1-Restricted T Cells
复制标题
DOI：
10.1016/j.chembiol.2008.11.008
复制
发表时间：
2009-01-30
影响因子：
--
通讯作者：
Gilleron, Martine
中科院分区：
文献类型：
--
作者：
Layre, Emilie;Collmann, Anthony;Gilleron, Martine
CD 1-限制性脂质特异性T淋巴细胞在结核分枝杆菌（结核病的病原体）感染期间启动。在这里，我们描述了单霉菌酸甘油酯（GroMM）的抗原性，它刺激CD 1b限制性CD 4（+）T细胞克隆。该抗原的化学表征表明，它存在两种立体异构体，一种合成异构体比另一种更具刺激性。甘油的羟基基团和分枝菌酸长度对于触发T细胞应答至关重要。GroMM由M.结核病感染的树突状细胞，证明抗原可用于在自然感染期间呈递。离体实验表明，GroMM刺激来自接种疫苗或潜伏感染的健康供体的T细胞，但不刺激来自活动性结核病患者的细胞，这表明GroMM特异性T细胞在感染期间被引发，并且它们的检测与缺乏临床活动性疾病相关。
CD1-restricted lipid-specific T lymphocytes are primed during infection with Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we describe the antigenicity of glycerol monomycolate (GroMM), which stimulates CD1b-restricted CD4(+) T cell clones. Chemical characterization of this antigen showed that it exists as two stereoisomers, one synthetic isomer being more stimulatory than the other. The hydroxyl groups of glycerol and the mycolic acid length are critical for triggering the T cell responses. GroMM was presented by M. tuberculosis- infected dendritic cells, demonstrating that the antigen is available for presentation during natural infection. Ex vivo experiments showed that GroMM stimulated T cells from vaccinated or latently infected healthy donors but not cells from patients with active tuberculosis, suggesting that GroMM-specific T cells are primed during infection and their detection correlates with lack of clinical active disease.