Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells1
Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells1
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分泌室和内体室参与向 II 型 NKT 细胞呈递外源自体糖脂1
作者：
K. Roy;I. Maričić;Archana Khurana;T. Smith;R. Halder;Vipin Kumar
自然杀伤 T (NKT) 细胞可识别 CD1 分子呈递的自身和外来脂质抗原。尽管海洋海绵来源的脂质 αGalCer 向 I 型 NKT 细胞的呈递已得到充分研究，但关于自身糖脂向 I 型或 II 型 NKT 细胞的呈递却知之甚少。在这里，我们研究了自身糖脂硫苷脂向 II 型 NKT 细胞的呈递，该细胞特异性识别单一种类的硫苷脂，即溶血硫苷脂，但不识别含有额外酰基链的其他硫苷脂。与其他硫苷脂或 αGalCer 相比，溶血硫苷脂与 CD1d 的结合亲和力较低。尽管板结合的 CD1d 在中性 pH 值下呈递溶血硫苷脂的效率较低，但在酸性 pH 值和存在 saposin C 的情况下，它可以有效呈递。 mCD1d 的溶酶体运输对于 αGalCer 呈递至 I 型 NKT 细胞是必需的，但对于将溶血硫苷脂呈递至 II 型 NKT 细胞而言并不重要。一致地，缺乏溶酶体脂质转移蛋白的 APC 有效地呈递溶血硫苷脂。溶血硫脑苷脂的呈递在伯氨喹、刀那霉素 A、莫能菌素、放线菌酮和微粒体甘油三酯转移蛋白抑制剂的存在下受到抑制，但在用布雷菲德菌素 A 处理后保持不变。渥曼青介导的脂质呈递抑制表明 PI-3 激酶在 mCD1d 运输中的重要作用。我们的数据总体表明，弱 CD1d 结合自糖脂配体（例如溶血硫苷脂）可以通过分泌区室和内体区室呈递。因此，这项研究为外源自体糖脂向 CD1d 限制性 T 细胞的呈递提供了重要的见解。
Natural Killer T (NKT) cells recognize both self and foreign lipid Ags presented by CD1 molecules. Although presentation of the marine sponge-derived lipid αGalCer to type I NKT cells has been well studied, little is known about self-glycolipid presentation to either type I or type II NKT cells. Here we have investigated presentation of the self-glycolipid sulfatide to a type II NKT cell that specifically recognizes a single species of sulfatide, namely lyso-sulfatide but not other sulfatides containing additional acyl chains. In comparison to other sulfatides or αGalCer, lyso-sulfatide binds with lower affinity to CD1d. Although plate-bound CD1d is inefficient in presenting lyso-sulfatide at neutral pH, it is efficiently presented at acidic pH and in the presence of saposin C. The lysosomal trafficking of mCD1d is required for αGalCer presentation to type I NKT cells, it is not important for presentation of lyso-sulfatide to type II NKT cells. Consistently, APCs deficient in a lysosomal lipid-transfer protein effectively present lyso-sulfatide. Presentation of lyso-sulfatide is inhibited in the presence of primaquine, concanamycin A, monensin, cycloheximide, and an inhibitor of microsomal triglyceride transfer protein but remains unchanged following treatment with brefeldin A. Wortmannin-mediated inhibition of lipid presentation indicates an important role for the PI-3kinase in mCD1d trafficking. Our data collectively suggest that weak CD1d-binding self-glycolipid ligands such as lyso-sulfatide can be presented via the secretory and endosomal compartments. Thus this study provides important insights into the exogenous self-glycolipid presentation to CD1d-restricted T cells.
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影响因子：
15.9
作者：
Halder, Ramesh C.;Aguilera, Carlos;Kumar, Vipin
通讯作者：
Kumar, Vipin
影响因子：
4.1
作者：
Hellyer, NJ;Cheng, K;Koland, JG
通讯作者：
Koland, JG
Wortmannin 是一种磷脂酰肌醇 3-激酶抑制剂，可阻断肽-MHC II 类复合物的组装。
影响因子：
4.4
作者：
Song,W;Wagle,NM;Banh,T;Whiteford,CC;Ulug,E;Pierce,SK
通讯作者：
Pierce,SK
溶酶体 LDL 衍生的胆固醇和质膜胆固醇易位至内质网进行酯化可能需要参与胆固醇从酸性区室（溶酶体/内体）排出的常见细胞因子。
DOI：
10.1016/0005-2760(94)00190-a
发表时间：
1995
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Spillane,DM;ReaganJr,JW;Kennedy,NJ;Schneider,DL;Chang,TY
通讯作者：
Chang,TY