3o8x

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Recognition of Glycolipid Antigen by iNKT Cell TCR

Structural highlights

3o8x is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.74Å
Ligands:FUC, GSL, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-alpha-dependent structural changes in the F' roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen alpha-galactosylceramide (alpha-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi alpha-galactosyl diacylglycerol-CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles alpha-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with alpha-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes.

The V{alpha}14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode.,Li Y, Girardi E, Wang J, Yu ED, Painter GF, Kronenberg M, Zajonc DM J Exp Med. 2010 Oct 4. PMID:20921281[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
26 reviews cite this structure
Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions.
Brennan et al. (2013)
25 more
35 other articles
No citations found

See Also

References

  1. ↑ Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity. 2001 Dec;15(6):897-908. PMID:11754812
  2. ↑ Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439 doi:10.1084/jem.20051625
  3. ↑ Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005 Aug;6(8):810-8. Epub 2005 Jul 10. PMID:16007091 doi:10.1038/ni1224
  4. ↑ Li Y, Girardi E, Wang J, Yu ED, Painter GF, Kronenberg M, Zajonc DM. The V{alpha}14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode. J Exp Med. 2010 Oct 4. PMID:20921281 doi:10.1084/jem.20101335

Contents


PDB ID 3o8x

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OCA

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