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

(2015) JOURNAL OF BIOLOGICAL CHEMISTRY. 290(28). p.17206-17217
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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.
Keywords
LIGAND, MOLECULAR-BASIS, BINDING, STIMULATION, protein crystallization, cytokine induction, glycolipid structure, immunology, GLYCOLIPIDS, TCR, RECOGNITION, HUMAN CD1D, NKT CELLS, ANTIGEN PRESENTATION

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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.
@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},
}

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