CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms
CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms
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DOI：
10.1016/j.cell.2023.08.022
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发表时间：
2023-10-12
期刊：
影响因子：
64.5
通讯作者：
Moody，D. Branch
中科院分区：
文献类型：
--
作者：
Huang，Shouxiong;Shahine，Adam;Moody，D. Branch
CD1 系统结合脂质抗原以展示给 T 细胞。在这里，我们解析了四种人类 CD1 抗原呈递分子的脂质组，提供了自脂质展示图。回答一个基本问题时，>2,000 个 CD1-脂质复合物的检测表明自鞘脂和磷脂的广泛存在。虽然肽抗原是经过化学处理的，但许多脂质以未改变的形式存在。然而，每种类型的 CD1 蛋白都会对自身脂质组进行差异性编辑，以根据脂质长度和化学成分显示不同的捕获基序，这表明了一般的抗原展示机制。对于 CD1a 和 CD1d，脂质大小与 CD1 裂隙体积相匹配。 CD1c 裂隙大小变化较大，而 CD1b 是异常值，其中配体和裂隙显示出极端的大小不匹配，这是通过在一个裂隙中均匀分布两个小脂质来解释的。此外，包含整合 CD1 脂质组的化合物列表支持了脂质阻滞剂和 T 细胞抗原的不断发现。
The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid display. Answering a basic question, the detection of >2,000 CD1-lipid complexes demonstrates broad presentation of self-sphingolipids and phospholipids. Whereas peptide antigens are chemically processed, many lipids are presented in an unaltered form. However, each type of CD1 protein differentially edits the self-lipidome to show distinct capture motifs based on lipid length and chemical composition, suggesting general antigen display mechanisms. For CD1a and CD1d, lipid size matches the CD1 cleft volume. CD1c cleft size is more variable, and CD1b is the outlier, where ligands and clefts show an extreme size mismatch that is explained by uniformly seating two small lipids in one cleft. Furthermore, the list of compounds that comprise the integrated CD1 lipidome supports the ongoing discovery of lipid blockers and antigens for T cells.