Abstract
Although T cells were previously believed to recognize only peptide antigen associated with the major histocompatibility complex (MHC), recent studies have shown that there are unique T cells specialized for recognition of lipid or glycolipid antigens bound to the MHC class I-like CD1 molecules (CD1a, b, c or d). Among these lipid-specific T cells, CD1d-restricted T cells, also referred to as natural killer (NK) T cells, are of special interest as a target of drug development, since their role in immunoregulation has been indicated in various physiological or disease conditions including autoimmunity. They are unique in their homogeneous ligand specificity for α-glycosylated sphingolipid and secrete large amounts of regulatory cytokines shortly after T cell receptor (TCR) engagement. The first glycolipid identified as an NKT cell ligand was α-galactosylceramide (α-GalCer) derived from marine sponges. α-GalCer exhibits significant immunomodulatory effects by stimulating NKT cells. However, we found that an altered analogue of α-GalCer with a shorter sphingosine chain (OCH), is more useful than α-GalCer for treatment of autoimmune disease models, because of its ability to selectively induce IL-4, a key cytokine for control of autoimmunity. As such, altered glycolipid ligands (AGL) of α-GalCer appear to be promising reagents for treatment of human autoimmune diseases.
Keywords: NKT Cell-Stimulating Synthetic Glycolipids, sphingosine, autoimmunity
Current Topics in Medicinal Chemistry
Title: NKT Cell-Stimulating Synthetic Glycolipids as Potential Therapeutics for Autoimmune Disease
Volume: 4 Issue: 5
Author(s): Takashi Yamamura, Katsuichi Miyamoto, Zsolt Illes, Endre Pal, Manabu Araki and Sachiko Miyake
Affiliation:
Keywords: NKT Cell-Stimulating Synthetic Glycolipids, sphingosine, autoimmunity
Abstract: Although T cells were previously believed to recognize only peptide antigen associated with the major histocompatibility complex (MHC), recent studies have shown that there are unique T cells specialized for recognition of lipid or glycolipid antigens bound to the MHC class I-like CD1 molecules (CD1a, b, c or d). Among these lipid-specific T cells, CD1d-restricted T cells, also referred to as natural killer (NK) T cells, are of special interest as a target of drug development, since their role in immunoregulation has been indicated in various physiological or disease conditions including autoimmunity. They are unique in their homogeneous ligand specificity for α-glycosylated sphingolipid and secrete large amounts of regulatory cytokines shortly after T cell receptor (TCR) engagement. The first glycolipid identified as an NKT cell ligand was α-galactosylceramide (α-GalCer) derived from marine sponges. α-GalCer exhibits significant immunomodulatory effects by stimulating NKT cells. However, we found that an altered analogue of α-GalCer with a shorter sphingosine chain (OCH), is more useful than α-GalCer for treatment of autoimmune disease models, because of its ability to selectively induce IL-4, a key cytokine for control of autoimmunity. As such, altered glycolipid ligands (AGL) of α-GalCer appear to be promising reagents for treatment of human autoimmune diseases.
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Cite this article as:
Yamamura Takashi, Miyamoto Katsuichi, Illes Zsolt, Pal Endre, Araki Manabu and Miyake Sachiko, NKT Cell-Stimulating Synthetic Glycolipids as Potential Therapeutics for Autoimmune Disease, Current Topics in Medicinal Chemistry 2004; 4 (5) . https://dx.doi.org/10.2174/1568026043451221
DOI https://dx.doi.org/10.2174/1568026043451221 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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