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

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journal contribution
posted on 2023-10-25, 05:04 authored by Shouxiong Huang, Adam Shahine, Tan-Yun Cheng, Yi-Ling Chen, Soo Weei Ng, Gautham R Balaji, Rachel Farquhar, Stephanie GrasStephanie Gras, Clare S Hardman, John D Altman, Nabil Tahiri, Adriaan J Minnaard, Graham S Ogg, Jacob A Mayfield, Jamie Rossjohn, D Branch Moody
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.


This work was supported by the NIH (AR048632, AI115358, and 75N93020D00005), the Wellcome Trust Collaborative Award (209222/Z/17/ Z), the American Lung Association (IA-629987), NHMRC (1128924, 1159272, and 2008981), the ARC (DE210101031), the Chinese Academy of Medical Sciences Innovation Fund for Medical Science (2018-I2M-2-002), the UK Medical Research Council, and the UKRI (MC_UU_00008).


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20p. (p. 4583-4596.e1–e6)





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© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (