The Identification of the Endogenous Ligands of Natural Killer T Cells Reveals the Presence of Mammalian α-Linked Glycosylceramides
| Autor: | Lisa, Kain, Bill, Webb, Brian L, Anderson, Shenglou, Deng, Marie, Holt, Anne, Costanzo, Anne, Constanzo, Meng, Zhao, Kevin, Self, Anais, Teyton, Chris, Everett, Mitchell, Kronenberg, Dirk M, Zajonc, Albert, Bendelac, Paul B, Savage, Luc, Teyton |
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| Rok vydání: | 2014 |
| Předmět: |
Ceramide
T-Lymphocytes Immunology Plasma protein binding Glucosylceramides Lymphocyte Activation Cell Line chemistry.chemical_compound Mice Immune system Antigen Animals Humans Immunology and Allergy B-Lymphocytes biology Natural killer T cell Sphingolipid Infectious Diseases chemistry Biochemistry Cell culture CD1D biology.protein Natural Killer T-Cells Antigens CD1d Glycolipids Protein Binding |
| Zdroj: | Immunity. 41:867 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2014.10.014 |
| Popis: | SummaryGlycosylceramides in mammalian species are thought to be present in the form of β-anomers. This conclusion was reinforced by the identification of only one glucosylceramide and one galactosylceramide synthase, both β-transferases, in mammalian genomes. Thus, the possibility that small amounts of α-anomers could be produced by an alternative enzymatic pathway, by an unfaithful enzyme, or spontaneously in unusual cellular compartments has not been examined in detail. We approached the question by taking advantage of the exquisite specificity of T and B lymphocytes and combined it with the specificity of catabolic enzymes of the sphingolipid pathway. Here, we demonstrate that mammalian immune cells produce constitutively very small quantities of α-glycosylceramides, which are the major endogenous ligands of natural killer T cells. Catabolic enzymes of the ceramide and glycolipid pathway tightly control the amount of these α-glycosylceramides. The exploitation of this pathway to manipulate the immune response will create new therapeutic opportunities. |
| Databáze: | OpenAIRE |
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