3TVM

Structure of the mouse CD1d-SMC124-iNKT TCR complex

Summary for 3TVM

• Entry DOI: 10.2210/pdb3tvm/pdb
• Related: 3RZC 3T1F 3TA3
• Descriptor: Antigen-presenting glycoprotein CD1d1, GLYCEROL, beta-2-microglobulin, ... (11 entities in total)
• Functional Keywords: antigen presentation, glycolipid, nkt cells, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 8
• Total formula weight: 193132.00

Authors

Girardi, E.,Li, Y.,Zajonc, D.M. (deposition date: 2011-09-20, release date: 2012-02-01, Last modification date: 2024-11-27)

Primary citation

Tyznik, A.J.,Farber, E.,Girardi, E.,Birkholz, A.,Li, Y.,Chitale, S.,So, R.,Arora, P.,Khurana, A.,Wang, J.,Porcelli, S.A.,Zajonc, D.M.,Kronenberg, M.,Howell, A.R.
Glycolipids that Elicit IFN-gama-Biased Responses from Natural Killer T Cells
Chem.Biol., 18:1620-1630, 2011

PubMed Abstract: Natural killer T (NKT) cells recognize glycolipids presented by CD1d. The first antigen described, α-galactosyl ceramide (αGalCer), is a potential anticancer agent whose activity depends upon IFN-γ secretion. We report two analogs of αGalCer based on a naturally occurring glycosphingolipid, plakoside A. These compounds induce enhanced IFN-γ that correlates with detergent-resistant binding to CD1d and an increased stability of the lipid-CD1d complexes on antigen-presenting cells. Structural analysis on one of the analogs indicates that it is more deeply bound inside the CD1d groove, suggesting tighter lipid-CD1d interactions. To our knowledge, this is the first example in which structural information provides an explanation for the increased lipid-CD1d stability, likely responsible for the Th1 bias. We provide insights into the mechanism of IFN-γ-inducing compounds, and because our compounds activate human NKT cells, they could have therapeutic utility.

PubMed: 22195564
DOI: 10.1016/j.chembiol.2011.10.015

Experimental method

X-RAY DIFFRACTION (2.8 Å)