小柯机器人

近日，澳大利亚莫纳什大学D. Branch Moody等研究人员合作发现，CD1脂质体揭示脂质结合模体和基于尺寸的抗原展示机制。这一研究成果于2023年9月18日在线发表在国际学术期刊《细胞》上。

研究人员解析了四种人类CD1抗原递呈分子的脂质体，并提供了自我脂质展示的图谱。在回答一个基本问题时，研究人员检测到了超过2000个CD1脂质复合物，这表明自鞘脂和磷脂的展示范围很广。肽抗原是经过化学处理的，而许多脂质是以未改变的形式呈现的。不过，每种CD1蛋白都会根据脂质的长度和化学成分对自身脂质体进行不同的编辑，从而显示出不同的捕获模体，这表明了通用的抗原展示机制。

对于CD1a和CD1d，脂质大小与CD1裂隙体积相匹配。CD1c裂隙的大小变化较大，而CD1b是一个离群点，配体和裂隙显示出极端的大小不匹配，这可以通过在一个裂隙中均匀地加入两个小脂质来解释。此外，组成综合CD1脂质体的化合物清单还有助于不断发现脂质阻断剂和T细胞抗原。

据悉，CD1系统能结合脂质抗原并向T细胞展示。

附：英文原文

Title: CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms

Author: Shouxiong Huang, Adam Shahine, Tan-Yun Cheng, Yi-Ling Chen, Soo Weei Ng, Gautham R. Balaji, Rachel Farquhar, Stephanie Gras, Clare S. Hardman, John D. Altman, Nabil Tahiri, Adriaan J. Minnaard, Graham S. Ogg, Jacob A. Mayfield, Jamie Rossjohn, D. Branch Moody

Issue&Volume: 2023-09-18

Abstract: 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.

DOI: 10.1016/j.cell.2023.08.022

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00912-1