Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity
Dirk M. Zajonc,Igor Maricic,Douglass Wu,Rarnesh Halder,Keshab Chandra Roy,Chi-Huey Wong,Vipin Kumar,Ian A. Wilson +7 more
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TLDR
The 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.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 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.read more
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Journal ArticleDOI
The biology of NKT cells.
TL;DR: NKT cell biology has emerged as a new field of research at the frontier between innate and adaptive immunity, providing a powerful model to study fundamental aspects of the cell and structural biology of glycolipid trafficking, processing, and recognition.
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Adenosine receptors: therapeutic aspects for inflammatory and immune diseases
TL;DR: This work has generated excitement regarding the potential use of adenosine-receptor-based therapies in the treatment of infection, autoimmunity, ischaemia and degenerative diseases.
Journal ArticleDOI
Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.
Yuki Kinjo,Emmanuel Tupin,Douglass Wu,Masakazu Fujio,Raquel Garcia-Navarro,Mohammed Rafii El Idrissi Benhnia,Mohammed Rafii El Idrissi Benhnia,Dirk M. Zajonc,Dirk M. Zajonc,Gil Ben-Menachem,Gary D. Ainge,Gavin F. Painter,Archana Khurana,Kasper Hoebe,Samuel M. Behar,Bruce Beutler,Ian A. Wilson,Moriya Tsuji,Timothy J. Sellati,Chi-Huey Wong,Mitchell Kronenberg +20 more
TL;DR: It is shown that mouse and human NKT cells also recognized glycolipids, specifically a diacylglycerol, from Borrelia burgdorferi, which causes Lyme disease, suggesting that NKT cell responses driven by T cell receptor–mediated glycolIPid recognition may provide protection against diverse pathogens.
Journal ArticleDOI
T cell antigen receptor recognition of antigen-presenting molecules.
Jamie Rossjohn,Stephanie Gras,John J. Miles,Stephen J. Turner,Dale I. Godfrey,James McCluskey +5 more
TL;DR: TCRs show remarkable structural and biological versatility in engaging different classes of Ag that are presented by polymorphic and monomorphic Ag-presenting molecules of the immune system.
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The role of NKT cells in tumor immunity.
Masaki Terabe,Jay A. Berzofsky +1 more
TL;DR: Because NKT cells respond rapidly, the balance along this axis can greatly influence other immune responses that follow, therefore, learning to manipulate the balanceAlong the NKT regulatory axis may be critical to devising successful immunotherapies for cancer.
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