Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 28, Pages 17206-17217Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.654814
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Funding
- United States Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- Department of Energy Office of Biological and Environmental Research
- National Institutes of Health from NIGMS [P41GM103393]
- Office of Science, Office of Basic Energy Sciences, United States Department of Energy [DE-AC02-05CH11231]
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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.
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