4y16

Publication Abstract from PubMed

The ability of different glycosphingolipids (GSLs) to activate Type I Natural Killer T cells (iNKT cells) has been known for two decades. The possible therapeutic use of these GSLs has been studied in many ways, however studies in which the efficacy of promising GSLs is compared under identical conditions are missing. Here we compare five unique GSLs structurally derived from alpha-galactosylceramide (alphaGalCer). 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. While all glycolipids are bound by the TCR 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.

Lipid and carbohydrate modifications of alpha-galactosylceramide differently influence mouse and human type I natural killer T cell activation.,Birkholz A, Nemcovic M, Yu ED, Girardi E, Wang J, Khurana A, Pauwels N, Farber E, Chitale S, Franck RW, Tsuji M, Howell A, Van Calenbergh S, Kronenberg M, Zajonc DM J Biol Chem. 2015 May 27. pii: jbc.M115.654814. PMID:26018083^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.