Lipid and Carbohydrate Modifications of α-Galactosylceramide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation
Year: 2015
Type: article
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 α-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 I NKT 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. Background: Several synthetic glycosphingolipids have been tested to determine their capacity to activate type I NKT cells. Results: Although the TCR binds with high affinity to all CD1d-presented glycolipids, only a few activate type I NKT cells in vivo . Conclusion: TCR binding affinity does not necessarily predict antigenicity in vivo . Significance: The prediction of the therapeutic efficacy of type I NKT cell antigens requires complementary assays.
Source: Journal of Biological Chemistry
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: U.S. Department of Energy, Fonds Wetenschappelijk Onderzoek, Universiteit Gent, Vlaamse regering, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Basic Energy Sciences, Biological and Environmental Research, SLAC National Accelerator Laboratory
Awards: G1229526393, Structural Immunology of CD1 and CD1-TCR Complexes, G1286236842, G1286251239, G1337544421, G1414775356, G1445641779, G1451874870, G155329293, G1581387393, G1804828992, G1816284028, G1831385526, Structure and function of peptide presentation by CD1d, Development and Function of NKT Cells, G223002938, G2371548206, G2539837713, G262532246, G303061748, G30714459, G3083819904, G315621713, G3432487278, G3488436650, G3629260272, G3636172902, G365575497, G382641700, G419881185, G4235786860, G4280418065, G42916606, G4501827968, G4581610328, G4908923434, G495301720, G498139845, CD1d/NKT-binding glycolipids in enhancing the immunogenicity of a malaria vaccine, G5570207115, G5849692847, Harnessing NKT Cell Activation by Glycolipids, G628751139, G650090426, G6550344761, G7083997402, G7283024673, G7313278570, Differentiation of subsets of NKT cells, G7787287669, G805243471, G8382000481, A Synchrotron Radiation Structural Biology Resource, Recognition of bacterial antigens by NKT cells, G8925327636, G9000010011, G9000083103, G9000162587, G9000215746, G9000240067, G911061179, G969889393
OpenAlex ID: W1893857266