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Immunity. 2014 Oct 16;41(4):543-54. doi: 10.1016/j.immuni.2014.08.017.

The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian α-linked glycosylceramides.

Author information

1
Department of Immunology and Microbial Science, the Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Molecular Biology, the Scripps Research Institute, La Jolla, CA 92037, USA.
3
Department of Chemistry, Brigham Young University, Provo, UT 84602, USA.
4
La Jolla Institute for Allergy & Immunology, La Jolla, CA 92037, USA.
5
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
6
Department of Immunology and Microbial Science, the Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: lteyton@scripps.edu.

Erratum in

  • Immunity. 2014 Nov 20;41(5):867. Constanzo, Anne [corrected to Costanzo, Anne].

Abstract

Glycosylceramides 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.

PMID:
25367571
PMCID:
PMC4220304
DOI:
10.1016/j.immuni.2014.08.017
[Indexed for MEDLINE]
Free PMC Article

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