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Lipid and carbohydrate modifications of α-galactosylcer-amide differently influence mouse and human type I natural killer T cell activation

Alysia Birkholz, Marek Nemčovič, Esther Dawen Yu, Enrico Girardi, Jing Wang, Archana Khurana, Nora Pauwels, Elisa Farber, Sampada Chitale, Richard W Franck, et al. (2015) JOURNAL OF BIOLOGICAL CHEMISTRY. 290(28). p.17206-17217
abstract
The ability of different glycosphingolipids (GSLs) to activate type I natural killer T cells (NKT cells) has been known for 2 decades. The possible therapeutic use of these GSLs has been studied in many ways; however, studies are needed in which the efficacy of promising GSLs is compared under identical conditions. Here, we compare five unique GSLs structurally derived from alpha-galactosylceramide. We employed biophysical and biological assays, as well as x-ray crystallography to study the impact of the chemical modifications of the antigen on type I NKT cell activation. Although all glycolipids are bound by the T cell receptor of type I NKT cells in real time binding assays with high affinity, only a few activate type INKT cells in in vivo or in vitro experiments. The differences in biological responses are likely a result of different pharmacokinetic properties of each lipid, which carry modifications at different parts of the molecule. Our results indicate a need to perform a variety of assays to ascertain the therapeutic potential of type I NKT cell GSL activators.
Please use this url to cite or link to this publication:
author
organization
alternative title
Lipid and carbohydrate modifications of alpha-galactosylcer-amide differently influence mouse and human type I natural killer T cell activation
year
type
journalArticle (original)
publication status
published
subject
keyword
LIGAND, MOLECULAR-BASIS, BINDING, STIMULATION, protein crystallization, cytokine induction, glycolipid structure, immunology, GLYCOLIPIDS, TCR, RECOGNITION, HUMAN CD1D, NKT CELLS, ANTIGEN PRESENTATION
journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
J. Biol. Chem.
volume
290
issue
28
pages
17206 - 17217
Web of Science type
Article
Web of Science id
000357730900017
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
4.258 (2015)
JCR rank
71/289 (2015)
JCR quartile
1 (2015)
ISSN
0021-9258
DOI
10.1074/jbc.M115.654814
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
6935315
handle
http://hdl.handle.net/1854/LU-6935315
date created
2015-09-22 10:10:20
date last changed
2016-12-19 15:38:56
@article{6935315,
  abstract     = {The ability of different glycosphingolipids (GSLs) to activate type I natural killer T cells (NKT cells) has been known for 2 decades. The possible therapeutic use of these GSLs has been studied in many ways; however, studies are needed in which the efficacy of promising GSLs is compared under identical conditions. Here, we compare five unique GSLs structurally derived from alpha-galactosylceramide. We employed biophysical and biological assays, as well as x-ray crystallography to study the impact of the chemical modifications of the antigen on type I NKT cell activation. Although all glycolipids are bound by the T cell receptor of type I NKT cells in real time binding assays with high affinity, only a few activate type INKT cells in in vivo or in vitro experiments. The differences in biological responses are likely a result of different pharmacokinetic properties of each lipid, which carry modifications at different parts of the molecule. Our results indicate a need to perform a variety of assays to ascertain the therapeutic potential of type I NKT cell GSL activators.},
  author       = {Birkholz, Alysia and Nem\v{c}ovi\v{c}, Marek and Yu, Esther Dawen and Girardi, Enrico and Wang, Jing and Khurana, Archana and Pauwels, Nora and Farber, Elisa and Chitale, Sampada and Franck, Richard W and Tsuji, Moriya and Howell, Amy and Van Calenbergh, Serge and Kronenberg, Mitchell and Zajonc, Dirk},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {LIGAND,MOLECULAR-BASIS,BINDING,STIMULATION,protein crystallization,cytokine induction,glycolipid structure,immunology,GLYCOLIPIDS,TCR,RECOGNITION,HUMAN CD1D,NKT CELLS,ANTIGEN PRESENTATION},
  language     = {eng},
  number       = {28},
  pages        = {17206--17217},
  title        = {Lipid and carbohydrate modifications of \ensuremath{\alpha}-galactosylcer-amide differently influence mouse and human type I natural killer T cell activation},
  url          = {http://dx.doi.org/10.1074/jbc.M115.654814},
  volume       = {290},
  year         = {2015},
}

Chicago
Birkholz, Alysia, Marek Nemčovič, Esther Dawen Yu, Enrico Girardi, Jing Wang, Archana Khurana, Nora Pauwels, et al. 2015. “Lipid and Carbohydrate Modifications of Α-galactosylcer-amide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation.” Journal of Biological Chemistry 290 (28): 17206–17217.
APA
Birkholz, A., Nemčovič, M., Yu, E. D., Girardi, E., Wang, J., Khurana, A., Pauwels, N., et al. (2015). Lipid and carbohydrate modifications of α-galactosylcer-amide differently influence mouse and human type I natural killer T cell activation. JOURNAL OF BIOLOGICAL CHEMISTRY, 290(28), 17206–17217.
Vancouver
1.
Birkholz A, Nemčovič M, Yu ED, Girardi E, Wang J, Khurana A, et al. Lipid and carbohydrate modifications of α-galactosylcer-amide differently influence mouse and human type I natural killer T cell activation. JOURNAL OF BIOLOGICAL CHEMISTRY. 2015;290(28):17206–17.
MLA
Birkholz, Alysia, Marek Nemčovič, Esther Dawen Yu, et al. “Lipid and Carbohydrate Modifications of Α-galactosylcer-amide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation.” JOURNAL OF BIOLOGICAL CHEMISTRY 290.28 (2015): 17206–17217. Print.