Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation

J Immunol. 2005 Jul 15;175(2):977-84. doi: 10.4049/jimmunol.175.2.977.


NKT cells are immunoregulatory lymphocytes whose activation is triggered by the recognition of lipid Ags in the context of the CD1d molecules by the TCR. In this study we present the crystal structure to 2.8 A of mouse CD1d bound to phosphatidylcholine. The interactions between the ligand acyl chains and the CD1d molecule define the structural and chemical requirements for the binding of lipid Ags to CD1d. The orientation of the polar headgroup toward the C terminus of the alpha1 helix provides a rationale for the structural basis for the observed Valpha chain bias in invariant NKT cells. The contribution of the ligand to the protein surface suggests a likely mode of recognition of lipid Ags by the NKT cell TCR.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD1 / chemistry*
  • Antigens, CD1 / immunology*
  • Antigens, CD1 / metabolism
  • Antigens, CD1d
  • Cell Line
  • Complementarity Determining Regions / metabolism
  • Crystallography, X-Ray
  • Drosophila melanogaster
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Ligands
  • Lymphocyte Activation / immunology*
  • Mice
  • Models, Molecular
  • Phosphatidylcholines / chemistry*
  • Phosphatidylcholines / immunology*
  • Phosphatidylcholines / metabolism
  • Protein Binding / immunology
  • Protein Isoforms / chemistry
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Surface Properties
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Antigens, CD1
  • Antigens, CD1d
  • Complementarity Determining Regions
  • Ligands
  • Phosphatidylcholines
  • Protein Isoforms
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Proteins

Associated data

  • PDB/1ZHN