The roles of 3' and 4' hydroxy groups in alpha-galactosylceramide stimulation of invariant natural killer T cells.
Chengfeng Xia,Chengfeng Xia,Wenpeng Zhang,Yalong Zhang,Wenlan Chen,Janos Nadas,Ryan Severin,Robert Woodward,Bin Wang,Xin Wang,Mitchell Kronenberg,Peng George Wang +11 more
TL;DR: It is discovered that the 3′ hydroxyl is very crucial in maintaining the molecule’s immunogenicity and any modification on this position will lead to the losing of activity.
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Abstract: The marine-derived α-galactosylceramide is an exogenous ligand for natural killer T cells and leads to the secretion of both T help 1 (Th1) and Th2 cytokines. The relationship between the sugar moiety structure and invariant natural killer T (iNKT) cell stimulation ability has not been fully understood. With the series α-galactosylceramide analogues varied on C3′ and C4′ position, subjected to a murine system, we discovered that the 3′ hydroxyl is very crucial in maintaining the molecule’s immunogenicity. Any modification on this position will lead to the losing of activity. We also found that the C4′ position is not so sensitive and can tolerate some small modifications on it. Moreover, the C4′ substituted analogues induced biased Th2 cytokines release was observed.
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Citations
Switching Invariant Natural Killer T (iNKT) Cell Response from Anticancerous to Anti-Inflammatory Effect: Molecular Bases
Xavier Laurent,Benjamin Bertin,Nicolas Renault,Amaury Farce,Silvia Speca,Ophélie Milhomme,Régis Millet,Pierre Desreumaux,Eric Henon,Philippe Chavatte +9 more
TL;DR: An up-to-date analysis of iNKT activators associated with a structure-activity relationship (SAR) study aimed at complementing available reviews by highlighting molecular bases for a selective immune response.
75
Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.
William C. Florence,Chengfeng Xia,Laura E. Gordy,Wenlan Chen,Yalong Zhang,James P. Scott-Browne,Yuki Kinjo,Karl O.A. Yu,Santosh Keshipeddy,Daniel G. Pellicci,Onisha Patel,Lars Kjer-Nielsen,James McCluskey,Dale I. Godfrey,Jamie Rossjohn,Stewart K. Richardson,Steven A. Porcelli,Amy R. Howell,Kyoko Hayakawa,Laurent Gapin,Dirk M. Zajonc,Peng George Wang,Sebastian Joyce +22 more
TL;DR: The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognizes structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule as discussed by the authors.
Structure-activity relationship studies of novel glycosphingolipids that stimulate natural killer T-cells.
TL;DR: A large number of analogs of KRN7000 show potent bioactivities and have the potential of being utilized as therapeutic agents, and structure-activity relationship studies of novel glycolipids which stimulate NKT cells efficiently are summarized.
39
Synthetic iNKT cell-agonists as vaccine adjuvants--finding the balance
TL;DR: This article explores strategies being investigated as means of increasing the specificity of and controlling the magnitude of the immune response generated by activation of iNKT cells with synthetic agonists.
38
References
CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.
Tetsu Kawano,Junqing Cui,Yasuhiko Koezuka,Isao Toura,Yoshikatsu Kaneko,Kazuhiro Motoki,Hitomi Ueno,Ryusuke Nakagawa,Hiroshi Sato,Eisuke Kondo,Haruhiko Koseki,Masaru Taniguchi +11 more
TL;DR: Glycosylceramide-mediated proliferative responses of Valpha14 NKT cells were abrogated by treatment with chloroquine-concanamycin A or by monoclonal antibodies against CD1d/Vbeta8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein.
2.5K
MOUSE CD1-SPECIFIC NK1 T CELLS: Development, Specificity, and Function
TL;DR: The specificity and function of mouse NK1 T cells are reviewed, the relationship of this lineage to mainstream T cells and NK cells is discussed, and the novel regulatory pathway, which straddles the innate and the adaptive immune systems, is discussed.
1.3K
Recognition of bacterial glycosphingolipids by natural killer T cells
Yuki Kinjo,Douglass Wu,Gisen Kim,Guo-Wen Xing,Michael A. Poles,Michael A. Poles,David D. Ho,Moriya Tsuji,Moriya Tsuji,Kazuyoshi Kawahara,Chi-Huey Wong,Mitchell Kronenberg +11 more
TL;DR: It is shown that most mouse and human NKT cells recognize glycosphingolipids from Sphingomonas, Gram-negative bacteria that do not contain lipopolysaccharide, and that these cells might be useful in providing protection from bacteria that cannot be detected by pattern recognition receptors such as Toll-like receptor 4.
974
A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells.
TL;DR: A synthetic glycolipid ligand for CD1d-restricted natural killer T (NKT) cells expressing the semi-invariant T-cell receptor (Vα14+) is preventive against EAE and targeting NKT cells with this ligand may be an attractive means for intervening in human autoimmune diseases such as multiple sclerosis.
954
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.
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