Lipid length controls antigen entry into endosomal and nonendosomal pathways for CDIb presentation
Lipid length controls antigen entry into endosomal and nonendosomal pathways for CDIb presentation
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DOI：
10.1038/ni780
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发表时间：
2002-05-01
影响因子：
30.5
通讯作者：
Porcelli, SA
中科院分区：
文献类型：
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作者：
Moody, DB;Briken, V;Porcelli, SA
CD I蛋白向T细胞呈递各种糖脂抗原，但控制哪些特定糖脂产生T细胞反应的细胞机制尚不清楚。我们在此表明，T细胞对具有长(C-80)烷基链的葡萄糖单菌酸抗原的识别涉及在需要几个小时的过程中将CD Ib蛋白和抗原递送至晚期内体。相反，具有较短(C-32)烷基链的相同抗原的类似物由细胞表面CD Ib蛋白快速但低效地呈递。树突状细胞（DC）优先呈递长链糖脂，部分原因是它们的快速内化和选择性地将抗原递送至内体区室。然而，非专业抗原呈递细胞优先呈递短链糖脂，因为它们缺乏显着的内体呈递途径。由于长烷基链长度将某些微生物糖脂与常见哺乳动物糖脂区分开来，因此这些发现表明树突状细胞使用专门的内体装载途径来促进优先识别具有更多内在异质结构的糖脂。
CD I proteins present various glycolipid antigens to T cells, but the cellular mechanisms that control which particular glycolipids generate T cell responses are not understood. We show here that T cell recognition of glucose monomycolate antigens with long (C-80) alkyl chains involves the delivery of CD Ib proteins and antigens to late endosomes in a process that takes several hours. In contrast, analogs of the same antigen with shorter (C-32) alkyl chains are rapidly, but inefficiently, presented by cell surface CD Ib proteins. Dendritic cells (DCs) preferentially present long-chain glycolipids, which results, in part, from their rapid internalization and selective delivery of antigens to endosomal compartments. Nonprofessional antigen-presenting cells, however, preferentially present short-chain glycolipids because of their lack of prominent endosomal presentation pathways. Because long alkyl chain length distinguishes certain microbial glycolipids from common mammalian glycolipids, these findings suggest that DCs use a specialized endosomal-loading pathway to promote preferential recognition of glycolipids with a more intrinsically foreign structure.