4IRJ: Structure Of The Mouse Cd1d-4clphc-alpha-galcer-inkt Tcr Complex

Citation:
Abstract
NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. Although it was previously thought that recognition of glycolipids such as alpha-galactosylceramide (alpha-GalCer) by the NKT cell TCR (NKTCR) obeys a key-lock principle, it is now clear this interaction is much more flexible. In this article, we report the structure-function analysis of a series of novel 6''-OH analogs of alpha-GalCer with more potent antitumor characteristics. Surprisingly, one of the novel carbamate analogs, alpha-GalCer-6''-(pyridin-4-yl)carbamate, formed novel interactions with the NKTCR. This interaction was associated with an extremely high level of Th1 polarization and superior antitumor responses. These data highlight the in vivo relevance of adding aromatic moieties to the 6''-OH position of the sugar and additionally show that judiciously chosen linkers are a promising strategy to generate strong Th1-polarizing glycolipids through increased binding either to CD1d or to NKTCR.
PDB ID: 4IRJDownload
MMDB ID: 112998
PDB Deposition Date: 2013/1/14
Updated in MMDB: 2013/09
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 4IRJ: tetrameric; determined by author
Molecular Components in 4IRJ
Label Count Molecule
Proteins (4 molecules)
1
Antigen-presenting Glycoprotein Cd1d1(Gene symbol: Cd1d1)
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2m)
Molecule annotation
1
Valpha14 (Mouse Variable Domain, Human Constant Domain)
Molecule annotation
1
Vbeta8.2 (Mouse Variable Domain, Human Constant Domain)
Molecule annotation
Chemicals (6 molecules)
1
4
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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