Projects per year
Abstract
CD1 proteins are expressed on dendritic cells, where they display lipid antigens to T-cell receptors (TCRs). Here we describe T-cell autoreactivity towards ubiquitous human membrane phospholipids presented by CD1b. These T-cells discriminate between two major types of lipids, sphingolipids and phospholipids, but were broadly cross-reactive towards diverse phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine. The crystal structure of a representative TCR bound to CD1b-phosphatidylcholine provides a molecular mechanism for this promiscuous recognition. We observe a lateral escape channel in the TCR, which shunted phospholipid head groups sideways along the CD1b-TCR interface, without contacting the TCR. Instead the TCR recognition site involved the neck region phosphate that is common to all major self-phospholipids but absent in sphingolipids. Whereas prior studies have focused on foreign lipids or rare self-lipids, we define a new molecular mechanism of promiscuous recognition of common self-phospholipids including those that are known targets in human autoimmune disease.
Original language | English |
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Article number | 56 |
Number of pages | 12 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 4 Jan 2019 |
Keywords
- immune tolerance
- immunology
- structural biology
- T-cell receptor
Projects
- 1 Finished
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ARC Centre of Excellence in Advanced Molecular Imaging
Whisstock, J., Abbey, B., Nugent, K., Quiney, H. M., Godfrey, D. I., Heath, W., Fairlie, D., Chapman, H., Peele, A., Davey, J. & Wittmann, A.
30/06/14 → 31/03/21
Project: Research
Prizes
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Robert Porter Early Career Researcher Publication Prize for Laboratory Based Sciences
Shahine, Adam (Recipient), 17 Aug 2020
Prize: Prize (including medals and awards)