T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids

Wun, K.S.; Reijneveld, Josephine F.; Cheng, Tan Yun; Ladell, Kristin; Uldrich, Adam P.; Nours, Jérôme Le; Miners, Kelly L.; McLaren, James E.; Grant, Emma J.; Haigh, Oscar; Watkins, Thomas S.; Suliman, Sara; Iwany, Sarah K.; Jiménez, Judith; Calderón, Róger; Tamara, Kattya Lopez; León, Segundo R.; Murray, Megan; Mayfield, Jacob A.; Altman, John D.; Purcell, Anthony W.; Miles, John J.; Godfrey, Dale I.; Gras, Stéphanie; Price, David A.; Rhijn, Ildiko Van; Moody, D. Branch; Rossjohn, Jamie

doi:10.1038/s41590-018-0065-7

Cited by 55 publications

(80 citation statements)

References 56 publications

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“…Next, we sought to identify and remove false positive or redundant signals. Building on previously reported methods for analysis of protein-lipid complexes (31–33), we implemented data filters for lipids in protein-SMALP complexes. First, ions were considered highly Pma1-specific when signals were 10-fold higher than for SMA polymer alone.…”

Section: Resultsmentioning

confidence: 99%

Periprotein lipidomes ofSaccharomyces cerevisiaeprovide a flexible environment for conformational changes of membrane proteins

Klooster

Cheng

Sikkema

et al. 2020

Preprint

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AbstractYeast tolerates a low pH and high solvent concentrations. The permeability of the plasma membrane (PM) for small molecules is low and lateral diffusion of proteins is slow. These findings suggest a high degree of lipid order, which raises the question of how membrane proteins function in such an environment. The yeast PM is segregated into the Micro-Compartment-of-Can1 (MCC) and Pma1 (MCP), which have different lipid compositions. We extracted proteins from these microdomains via stoichiometric capture of lipids and proteins in styrene-maleic-acid-lipid-particles (SMALPs). We purified SMALP-lipid-protein complexes by chromatography and quantitatively analyzed periprotein lipids located within the diameter defined by one SMALP. Phospholipid and sterol concentrations are similar for MCC and MCP, but sphingolipids are enriched in MCP. Ergosterol is depleted from this periprotein lipidome, whereas phosphatidylserine is enriched relative to the bulk of the plasma membrane. Direct detection of PM lipids in the ‘periprotein space’ supports the conclusion that proteins function in the presence of a locally disordered lipid state.

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Section: Resultsmentioning

confidence: 99%

Periprotein lipidomes ofSaccharomyces cerevisiaeprovide a flexible environment for conformational changes of membrane proteins

Klooster

Cheng

Sikkema

et al. 2020

Preprint

Self Cite

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“…So this finding suggests that BC24A is a representative of the private T cell repertoire unique to this individual. Whereas CD1 tetramers typically bind TCRs, there is some prior evidence for staining of non‐T cells or binding to non‐TCR proteins like ILT4 . Therefore, to assess whether CD1b‐BbGL‐II tetramers bind this αβ TCR, we performed a TCR transfer experiment.…”

Section: Resultsmentioning

confidence: 99%

CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells

et al. 2019

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Lyme disease is a common multisystem disease caused by infection with a tick‐transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL‐II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL‐II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b‐BbGL‐II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL‐II‐like molecules using tetramers and activation assays revealed a concomitant response to CD1b‐expressing APCs in absence of BbGL‐II. Further, among all major classes of self‐lipid tested, BbGL‐II responsive TCRs show strong cross‐reactivity to diacylglycerol, a self‐lipid antigen with structural similarities to BbGL‐II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross‐reactive CD1b‐restricted T cell responses to bacterial and self‐antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross‐reactive T cells.

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“…Next we sought to identify and remove false positive or redundant signals. Building on previously reported methods for analysis of protein-lipid complexes(28–30), we implemented data filters for lipids in protein-SMALP complexes. First, ions were considered highly Pma1-specific when signals were 10-fold higher than for SMA polymer alone.…”

Section: Resultsmentioning

confidence: 99%

Periprotein membrane lipidomics and the role of lipids in transporter function in yeast

Cheng

et al. 2020

Preprint

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Impact statementMembrane protein-specific lipidomics provides information on the organization of the yeast plasma membrane and the functioning of solute transporters 2 Abstract 21 22The yeast plasma membrane is segregated into domains: the Micro-Compartment-of-Can1 (MCC) 23and Pma1 (MCP) have a different protein composition, but their lipid composition is largely 24 unknown. We extracted proteins residing in these microdomains via stoichiometric capture of lipids 25and proteins in styrene-maleic-acid-lipid-particles (SMALPs). We purified SMALPs by affinity 26 chromatography and quantitatively analyzed the lipids by mass spectrometry and their role in 27 transporter function. We found that phospholipid and sterol concentrations are similar for MCC and 28MCP, but sphingolipids are enriched in MCP. Ergosterol is depleted from the periprotein lipidome, 29whereas phosphatidylserine is enriched relative to the bulk of the plasma membrane. 30Phosphatidylserine, non-bilayer lipids and ergosterol are essential for activity of Lyp1; the 31 transporter also requires a balance of saturated/unsaturated fatty acids. We propose that proteins 32can function in the yeast plasma membrane by the disordered state of surrounded lipids and diffuse 33 slowly in domains of high lipid order. 34 35

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T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids

Cited by 55 publications

References 56 publications

Periprotein lipidomes ofSaccharomyces cerevisiaeprovide a flexible environment for conformational changes of membrane proteins

Periprotein lipidomes ofSaccharomyces cerevisiaeprovide a flexible environment for conformational changes of membrane proteins

CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells

Periprotein membrane lipidomics and the role of lipids in transporter function in yeast

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