Endogenous ligands of natural killer T cells are alpha-linked glycosylceramides

•The endogenous ligands of NKT cells are α-linked monoglycosylceramides.•α-Linked monoglycosylceramides were thought to be absent from mammalian lipidomes.•New tools have been built to study the chemical structure of glycolipids.•Availability of endogenous α-galactosylceramide is regulated by degrad...

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Veröffentlicht in:Molecular immunology Jg. 68; H. 2; S. 94 - 97
Hauptverfasser: Kain, Lisa, Costanzo, Anne, Webb, Bill, Holt, Marie, Bendelac, Albert, Savage, Paul B., Teyton, Luc
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Elsevier Ltd 01.12.2015
Schlagworte:
Animals
Anomers
Antigen Presentation - genetics
Antigen-Presenting Cells - cytology
Antigen-Presenting Cells - immunology
Antigens, CD1d - immunology
Antigens, CD1d - metabolism
bioassays
Ceramide
Ceramides - chemistry
Ceramides - classification
Ceramides - immunology
Ceramides - metabolism
chemical analysis
Contamination
Endogenous ligand
enzymes
Glucosyltransferases - genetics
Glucosyltransferases - immunology
Humans
Killer Cells, Natural - cytology
Killer Cells, Natural - immunology
ligands
mammals
N-Acylsphingosine Galactosyltransferase - genetics
N-Acylsphingosine Galactosyltransferase - immunology
NKT cells
T-lymphocytes
Thymic selection
Thymocytes - cytology
Thymocytes - immunology
Thymus Gland
Ceramide
Anomers
NKT cells
Thymic selection
Endogenous ligand
Contamination
ISSN:0161-5890, 1872-9142, 1872-9142
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Zusammenfassung:•The endogenous ligands of NKT cells are α-linked monoglycosylceramides.•α-Linked monoglycosylceramides were thought to be absent from mammalian lipidomes.•New tools have been built to study the chemical structure of glycolipids.•Availability of endogenous α-galactosylceramide is regulated by degradation. The nature of the endogenous ligands for natural killer T (NKT) cells has been debated for more than a decade. Because the mammalian glycosylceramide synthases are invertases, it is believed that in mammals all glycosylceramides are β anomers. However, the possibility that an alternative enzymatic pathway, an unfaithful enzyme, or unique physico-chemical environments could allow the production of small quantities of α anomers should be entertained. Classic biochemical and chemical analysis approaches are not well suited for this challenge as they lack sensitivity. Using a combination of biological assays and new technological approaches, we have unequivocally demonstrated that α glycosylceramides were constitutively produced by mammalian immune cells, loaded onto CD1d and presented to NKT cells both in the thymus and in the periphery. Their amount is controlled tightly by catabolic enzymes, and can be altered in vitro and in vivo to modify NKT cell behavior.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0161-5890
1872-9142
1872-9142
DOI:10.1016/j.molimm.2015.06.009