Non-classical MHC Class I molecule CD1d at 2.29Å resolution
Data provenance
Information sections
Complex type
Species
Locus / Allele group
Cardiolipin binds to CD1d and stimulates CD1d-restricted ���� T cells in the normal murine repertoire.
Cardiolipin (CL), a major phospholipid in bacterial cell walls, is sequestered from the immune system in mammalian mitochondria and is, therefore, a potential danger signal. Based on growing evidence that phospholipids constitute natural ligands for CD1 and that CD1d-restricted T cells recognize phospholipids, we hypothesized that CD1d binds and presents CL and that T cells in the normal immune repertoire respond to CL in a CD1d-restricted manner. We determined the murine CD1d-CL crystal structure at 2.3 Å resolution and established through additional lipid loading experiments that CL, a tetra-acylated phospholipid, binds to murine CD1d with two alkyl chains buried inside the CD1d binding groove and the remaining two exposed into the solvent. We furthermore demonstrate the functional stimulatory activity of CL, showing that splenic and hepatic γδ T cells from healthy mice proliferate in vitro in response to mammalian or bacterial CL in a dose-dependent and CD1d-restricted manner, rapidly secreting the cytokines IFN-γ and RANTES. Finally, we show that hepatic γδ T cells are activated in vivo by CD1d-bearing dendritic cells that have been pulsed with CL, but not phosphatidylcholine. Together, these findings demonstrate that CD1d is able to bind and present CL to a subset of CL-responsive γδ T cells that exist in the spleen and liver of healthy mice and suggest that these cells could play a role in host responses to bacterial lipids and, potentially, self-CL. We propose that CL-responsive γδ T cells play a role in immune surveillance during infection and tissue injury.
Structure deposition and release
Data provenance
Publication data retrieved from PDBe REST API8 and PMCe REST API9
Other structures from this publication
1. Beta 2 microglobulin
Beta 2 microglobulin
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10 20 30 40 50 60
IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDW 70 80 90 SFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM |
2. CD1d
CD1d
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10 20 30 40 50 60
SEAQQKNYTFRCLQMSSFANRSWSRTDSVVWLGDLQTHRWSNDSATISFTKPWSQGKLSN 70 80 90 100 110 120 QQWEKLQHMFQVYRVSFTRDIQELVKMMSPKEDYPIEIQLSAGCEMYPGNASESFLHVAF 130 140 150 160 170 180 QGKYVVRFWGTSWQTVPGAPSWLDLPIKVLNADQGTSATVQMLLNDTCPLFVRGLLEAGK 190 200 210 220 230 240 SDLEKQEKPVAWLSSVPSSAHGHRQLVCHVSGFYPKPVWVMWMRGDQEQQGTHRGDFLPN 250 260 270 280 ADETWYLQATLDVEAGEEAGLACRVKHSSLGGQDIILYWHHHHHH |
Data provenance
Sequences are retrieved via the Uniprot method of the RSCB REST API. Sequences are then compared to those derived from the PDB file and matched against sequences retrieved from the IPD-IMGT/HLA database for human sequences, or the IPD-MHC database for other species. Mouse sequences are matched against FASTA files from Uniprot. Sequences for the mature extracellular protein (signal petide and cytoplasmic tail removed) are compared to identical length sequences from the datasources mentioned before using either exact matching or Levenshtein distance based matching.
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Data license
Footnotes
- Protein Data Bank Europe - Coordinate Server
- 1HHK - HLA-A*02:01 binding LLFGYPVYV at 2.5Å resolution - PDB entry for 1HHK
- Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. - PyMol CEALIGN Method - Publication
- PyMol - PyMol.org/pymol
- Levenshtein distance - Wikipedia entry
- Protein Data Bank Europe REST API - Molecules endpoint
- 3Dmol.js: molecular visualization with WebGL - 3DMol.js - Publication
- Protein Data Bank Europe REST API - Publication endpoint
- PubMed Central Europe REST API - Articles endpoint

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