6cuh
Crystal structure of the unliganded BC8B TCRCrystal structure of the unliganded BC8B TCR
Structural highlights
Publication Abstract from PubMedCD1 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. A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids.,Shahine A, Reinink P, Reijneveld JF, Gras S, Holzheimer M, Cheng TY, Minnaard AJ, Altman JD, Lenz S, Prandi J, Kubler-Kielb J, Moody DB, Rossjohn J, Van Rhijn I Nat Commun. 2019 Jan 4;10(1):56. doi: 10.1038/s41467-018-07898-0. PMID:30610190[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||