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首页> 外文期刊>Infection and immunity >A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components
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A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components

机译：新型分枝杆菌糖脂成分激活保护性γ9δ2T细胞亚群。

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γ9δ2 T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ9δ2 T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ9δ2 T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ9δ2 T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ9δ2 T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ9δ2 T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.
机译：γ9δ2T细胞在先天免疫和适应性免疫之间建立了天然桥梁，对粘膜组织中的病原体感染快速有效地做出反应，并且由结核病（TB）感染和卡介苗（BCG）疫苗接种显着诱导。分枝杆菌扩增的γ9δ2T细胞仅代表磷酸抗原{异戊烯基焦磷酸[IPP]和（E）-4-羟基-3-甲基-丁-2-烯基焦磷酸[HMBPP]}响应的γ9δ2T细胞的一部分，表达寡克隆一组T细胞受体（TCR）序列，可更有效地识别和抑制细胞内结核分枝杆菌感染。基于此前提，我们一直在寻找能够诱导分枝杆菌保护性γ9δ2T细胞独特子集的结核分枝杆菌抗原。我们的筛选策略包括鉴定结核分枝杆菌级分，这些级分会扩增具有抑制细胞内分枝杆菌复制的生物学功能的γ9δ2T细胞。结核分枝杆菌全细胞裂解物（MtbWL）的化学处理排除了蛋白质，核酸和非极性脂质，因为结核分枝杆菌抗原可诱导保护性γ9δ2T细胞。温和的酸水解将复杂的碳水化合物转化为单体残基，废除了结核分枝杆菌全细胞裂解物的比活性，这表明生物活性需要多糖。用氯仿-甲醇-水（10：10：3​​）萃取MtbWL，得到极性脂质级分，具有很高的比活。该活性通过硅胶色谱进一步丰富。质谱分析和生物活性成分的核磁共振分析相结合，表明含6-O-甲基葡萄糖的脂多糖（mGLP）是该活性成分中的主要成分。这些结果对开发新的预防和治疗结核病的免疫疗法具有重要意义。

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