A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Adam Shahine, Peter Reinink, Josephine F. Reijneveld, Stephanie Gras, Mira Holzheimer, Tan-Yun Cheng, Adriaan J. Minnaard, John D. Altman, Steffi Lenz, Jacques Prandi, Joanna Kubler-Kielb, D. Branch Moody, Jamie Rossjohn, Ildiko Van Rhijn

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. More... »

PAGES

56

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-07898-0

DOI

http://dx.doi.org/10.1038/s41467-018-07898-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111014667

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30610190


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