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. doi: 10.1084/jem.20051625. Epub 2005 Nov 28.


Sulfatide derived from the myelin stimulates a distinct population of CD1d-restricted natural killer T (NKT) cells. Cis-tetracosenoyl sulfatide is one of the immunodominant species in myelin as identified by proliferation, cytokine secretion, and CD1d tetramer staining. The crystal structure of mouse CD1d in complex with cis-tetracosenoyl sulfatide at 1.9 A resolution reveals that the longer cis-tetracosenoyl fatty acid chain fully occupies the A' pocket of the CD1d binding groove, whereas the sphingosine chain fills up the F' pocket. A precise hydrogen bond network in the center of the binding groove orients and positions the ceramide backbone for insertion of the lipid tails in their respective pockets. The 3'-sulfated galactose headgroup is highly exposed for presentation to the T cell receptor and projects up and away from the binding pocket due to its beta linkage, compared with the more intimate binding of the alpha-glactosyl ceramide headgroup to CD1d. These structure and binding data on sulfatide presentation by CD1d have important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation* / immunology
  • Antigens, CD1 / chemistry*
  • Antigens, CD1 / immunology
  • Antigens, CD1d
  • Autoimmunity* / immunology
  • Cattle
  • Cell Proliferation
  • Crystallography, X-Ray
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Galactosylceramides / chemistry
  • Galactosylceramides / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Knockout
  • Myelin Sheath / chemistry*
  • Myelin Sheath / immunology
  • Protein Structure, Tertiary
  • Sulfoglycosphingolipids / chemistry*
  • Sulfoglycosphingolipids / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Antigens, CD1
  • Antigens, CD1d
  • Cytokines
  • Galactosylceramides
  • Sulfoglycosphingolipids