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3o8x

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Recognition of Glycolipid Antigen by iNKT Cell TCRRecognition of Glycolipid Antigen by iNKT Cell TCR

Structural highlights

3o8x is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Gene:Cd1.1, CD1d, Cd1d1 (LK3 transgenic mice), B2m, beta-2-microglobulin, mCG_11606, RP23-34E24.5-001 (LK3 transgenic mice), TRAC, TCRA (LK3 transgenic mice), TRBC2, TCRBC2 (LK3 transgenic mice)
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] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.

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.

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

3o8x, resolution 2.74Å

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