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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| Published in: | Molecular immunology Vol. 68; no. 2; pp. 94 - 97 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier Ltd
01.12.2015
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| ISSN: | 0161-5890, 1872-9142, 1872-9142 |
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| Abstract | •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. |
|---|---|
| AbstractList | •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. 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 physic-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. 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. 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.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. |
| Author | Teyton, Luc Costanzo, Anne Webb, Bill Savage, Paul B. Kain, Lisa Holt, Marie Bendelac, Albert |
| AuthorAffiliation | 3 University of Chicago, Committee on Immunology, Chicago, IL 60637, USA 2 Department of Molecular Biology, La Jolla, CA 92037, USA 4 Brigham Young University, Department of Chemistry, Brigham Young University, Provo, UT 84602, USA 1 The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA |
| AuthorAffiliation_xml | – name: 2 Department of Molecular Biology, La Jolla, CA 92037, USA – name: 1 The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA – name: 3 University of Chicago, Committee on Immunology, Chicago, IL 60637, USA – name: 4 Brigham Young University, Department of Chemistry, Brigham Young University, Provo, UT 84602, USA |
| Author_xml | – sequence: 1 givenname: Lisa surname: Kain fullname: Kain, Lisa organization: The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA – sequence: 2 givenname: Anne surname: Costanzo fullname: Costanzo, Anne organization: The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA – sequence: 3 givenname: Bill surname: Webb fullname: Webb, Bill organization: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 4 givenname: Marie surname: Holt fullname: Holt, Marie organization: The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA – sequence: 5 givenname: Albert surname: Bendelac fullname: Bendelac, Albert organization: University of Chicago, Committee on Immunology, Chicago, IL 60637, USA – sequence: 6 givenname: Paul B. surname: Savage fullname: Savage, Paul B. organization: Brigham Young University, Department of Chemistry, Brigham Young University, Provo, UT 84602, USA – sequence: 7 givenname: Luc surname: Teyton fullname: Teyton, Luc email: lteyton@scripps.edu organization: The Scripps Research Institute, Department of Immunology and Microbial Science, La Jolla, CA 92037, USA |
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| Cites_doi | 10.1016/j.immuni.2014.08.017 10.1038/nature03408 10.1042/bj1240713 10.1038/ni.2143 10.1016/j.immuni.2010.08.003 10.1073/pnas.1833166100 10.1073/pnas.1415357111 10.1038/ni.2245 10.1146/annurev.immunol.22.012703.104608 10.1146/annurev.biochem.76.061005.092322 10.1126/science.1103440 10.1146/annurev.immunol.25.022106.141711 |
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| Keywords | Ceramide Anomers NKT cells Thymic selection Endogenous ligand Contamination |
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| SubjectTerms | 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 |
| Title | Endogenous ligands of natural killer T cells are alpha-linked glycosylceramides |
| URI | https://dx.doi.org/10.1016/j.molimm.2015.06.009 https://www.ncbi.nlm.nih.gov/pubmed/26141240 https://www.proquest.com/docview/1727993779 https://www.proquest.com/docview/2000436223 https://pubmed.ncbi.nlm.nih.gov/PMC4624034 |
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