Epitopes described in "Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity."

Article Authors:Dirk M Zajonc; Igor Maricic; Douglass Wu; Ramesh Halder; Keshab Roy; Chi-Huey Wong; Vipin Kumar; Ian A Wilson
Article Title:Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity.
Reference Detail
Reference ID:1012870
Abstract: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.
Affiliations:Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Reference Type:Literature
PubMed ID:16314439
Journal:J Exp Med
Journal Volume:202
Article Pages:1517-26
Journal ISSN:0022-1007
Article Chemical List:Antigens, CD1;Antigens, CD1d;Cytokines;Galactosylceramides;Sulfoglycosphingolipids
Article MeSH List:Animals; Antigen Presentation(immunology); Antigens, CD1(chemistry; immunology); Antigens, CD1d; Autoimmunity(immunology); Cattle; Cell Proliferation; Crystallography, X-Ray; Cytokines(immunology; secretion); Female; Galactosylceramides(chemistry; immunology); Killer Cells, Natural(immunology; secretion); Mice; Mice, Knockout; Myelin Sheath(chemistry; immunology); Protein Structure, Tertiary; Sulfoglycosphingolipids(chemistry; immunology); T-Lymphocytes(immunology; secretion)
Curation Last Updated:2016-04-11 20:59:22