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A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids
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 phosp...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320368/ https://www.ncbi.nlm.nih.gov/pubmed/30610190 http://dx.doi.org/10.1038/s41467-018-07898-0 |
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author | Shahine, Adam Reinink, Peter Reijneveld, Josephine F. Gras, Stephanie Holzheimer, Mira Cheng, Tan-Yun Minnaard, Adriaan J. Altman, John D. Lenz, Steffi Prandi, Jacques Kubler-Kielb, Joanna Moody, D. Branch Rossjohn, Jamie Van Rhijn, Ildiko |
author_facet | Shahine, Adam Reinink, Peter Reijneveld, Josephine F. Gras, Stephanie Holzheimer, Mira Cheng, Tan-Yun Minnaard, Adriaan J. Altman, John D. Lenz, Steffi Prandi, Jacques Kubler-Kielb, Joanna Moody, D. Branch Rossjohn, Jamie Van Rhijn, Ildiko |
author_sort | Shahine, Adam |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6320368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63203682019-01-07 A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids Shahine, Adam Reinink, Peter Reijneveld, Josephine F. Gras, Stephanie Holzheimer, Mira Cheng, Tan-Yun Minnaard, Adriaan J. Altman, John D. Lenz, Steffi Prandi, Jacques Kubler-Kielb, Joanna Moody, D. Branch Rossjohn, Jamie Van Rhijn, Ildiko Nat Commun Article 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. Nature Publishing Group UK 2019-01-04 /pmc/articles/PMC6320368/ /pubmed/30610190 http://dx.doi.org/10.1038/s41467-018-07898-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shahine, Adam Reinink, Peter Reijneveld, Josephine F. Gras, Stephanie Holzheimer, Mira Cheng, Tan-Yun Minnaard, Adriaan J. Altman, John D. Lenz, Steffi Prandi, Jacques Kubler-Kielb, Joanna Moody, D. Branch Rossjohn, Jamie Van Rhijn, Ildiko A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids |
title | A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids |
title_full | A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids |
title_fullStr | A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids |
title_full_unstemmed | A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids |
title_short | A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids |
title_sort | t-cell receptor escape channel allows broad t-cell response to cd1b and membrane phospholipids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320368/ https://www.ncbi.nlm.nih.gov/pubmed/30610190 http://dx.doi.org/10.1038/s41467-018-07898-0 |
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