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 Å 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 β linkage, compared with the more intimate binding of the α-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.
Skip Nav Destination
Article navigation
5 December 2005
Article|
November 28 2005
Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity
Dirk M. Zajonc,
Dirk M. Zajonc
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037
Search for other works by this author on:
Igor Maricic,
Igor Maricic
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Search for other works by this author on:
Douglass Wu,
Douglass Wu
2Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037
3Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037
Search for other works by this author on:
Ramesh Halder,
Ramesh Halder
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Search for other works by this author on:
Keshab Roy,
Keshab Roy
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Search for other works by this author on:
Chi-Huey Wong,
Chi-Huey Wong
2Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037
3Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037
Search for other works by this author on:
Vipin Kumar,
Vipin Kumar
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Search for other works by this author on:
Ian A. Wilson
Ian A. Wilson
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037
3Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037
Search for other works by this author on:
Dirk M. Zajonc
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037
Igor Maricic
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Douglass Wu
2Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037
3Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037
Ramesh Halder
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Keshab Roy
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Chi-Huey Wong
2Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037
3Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037
Vipin Kumar
4Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
Ian A. Wilson
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037
3Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037
CORRESPONDENCE Ian A. Wilson: [email protected] OR Vipin Kumar: [email protected]
Abbreviations used: α-GalCer, α-galactosyl ceramide; CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; Endo H, Endoglycosidase H; iGB3, isoglobotrihexosyl ceramide; MS, multiple sclerosis; NKT, natural killer T; PC, phosphatidyl choline; SF9, Spodoptera frugiperda.
Received:
August 11 2005
Accepted:
October 27 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (11): 1517–1526.
Article history
Received:
August 11 2005
Accepted:
October 27 2005
Citation
Dirk M. Zajonc, Igor Maricic, Douglass Wu, Ramesh Halder, Keshab Roy, Chi-Huey Wong, Vipin Kumar, Ian A. Wilson; Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity . J Exp Med 5 December 2005; 202 (11): 1517–1526. doi: https://doi.org/10.1084/jem.20051625
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement