Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor

Nat Immunol. 2005 Aug;6(8):810-8. doi: 10.1038/ni1224. Epub 2005 Jul 10.


Natural killer T cells express a conserved, semi-invariant alphabeta T cell receptor that has specificity for self glycosphingolipids and microbial cell wall alpha-glycuronosylceramide antigens presented by CD1d molecules. Here we report the crystal structure of CD1d in complex with a short-chain synthetic variant of alpha-galactosylceramide at a resolution of 2.2 A. This structure elucidates the basis for the high specificity of these microbial ligands and explains the restriction of the alpha-linkage as a unique pathogen-specific pattern-recognition motif. Comparison of the binding of altered lipid ligands to CD1d and T cell receptors suggested that the differential T helper type 1-like and T helper type 2-like properties of natural killer T cells may originate largely from differences in their 'loading' in different cell types and hence in their tissue distribution in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antigens, CD1 / biosynthesis
  • Antigens, CD1d
  • Cell Wall / metabolism
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Galactosylceramides / chemistry
  • Glycosphingolipids / chemistry
  • Hot Temperature
  • Humans
  • Isoelectric Focusing
  • Killer Cells, Natural / chemistry
  • Killer Cells, Natural / immunology*
  • Ligands
  • Lipids / chemistry
  • Lymphocyte Activation
  • Mice
  • Models, Chemical
  • Models, Molecular
  • Mutation
  • Protein Conformation
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship
  • Surface Plasmon Resonance
  • Temperature
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Time Factors
  • Tissue Distribution


  • Antigens, CD1
  • Antigens, CD1d
  • CD1D protein, human
  • Galactosylceramides
  • Glycosphingolipids
  • Ligands
  • Lipids
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Proteins
  • alpha-galactosylceramide