@article{ec962d3e79c54e43aab46be48bb492db,
title = "Photoactivable Glycolipid Antigens Generate Stable Conjugates with CD1d for Invariant Natural Killer T Cell Activation",
abstract = "Activation of invariant natural killer T lymphocytes (iNKT cells) by α-galactosylceramide (α-GC) elicits a range of pro-inflammatory or anti-inflammatory immune responses. We report the synthesis and characterization of a series of α-GC analogues with acyl chains of varying length and a terminal benzophenone. These bound efficiently to the glycolipid antigen presenting protein CD1d, and upon photoactivation formed stable CD1d-glycolipid covalent conjugates. Conjugates of benzophenone α-GCs with soluble or cell-bound CD1d proteins retained potent iNKT cell activating properties, with biologic effects that were modulated by acyl chain length and the resulting affinities of conjugates for iNKT cell antigen receptors. Analysis by mass spectrometry identified a unique covalent attachment site for the glycolipid ligands in the hydrophobic ligand binding pocket of CD1d. The creation of covalent conjugates of CD1d with α-GC provides a new tool for probing the biology of glycolipid antigen presentation, as well as opportunities for developing effective immunotherapeutics.",
author = "Natacha Veerapen and Kharkwal, {Shalu Sharma} and Peter Jervis and Veemal Bhowruth and Besra, {Amareeta K.} and North, {Simon J.} and Haslam, {Stuart M.} and Anne Dell and Judith Hobrath and Quaid, {Padraic J.} and Moynihan, {Patrick J.} and Cox, {Liam R.} and Himanshu Kharkwal and Maurice Zauderer and Besra, {Gurdyal S.} and Porcelli, {Steven A.}",
note = "Funding Information: Major funding support was provided by NIH/NIAID grant R01 AI45889 and U01 GM111849 (to S.A.P.). G.S.B. acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick and a Royal Society Wolfson Research Merit Award. S.M.H and S.J.N. were supported by Biotechnology and Biological Sciences Research Council Grant BB/K016164/1. Funding Information: Major funding support was provided by NIH/NIAID grant R01 AI45889 and U01 GM111849 (to S.A.P.). G.S.B. acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick and a Royal Society Wolfson Research Merit Award. S.M.H and S.J.N. were supported by Biotechnology and Biological Sciences Research Council Grant BB/K016164/1. Flow cytometry and recombinant protein production were supported by core facilities of the Albert Einstein College of Medicine Cancer Center (NCI grant CA13330). We thank Drs. Alena Donda (Ludwig Cancer Institute) and Amy Howell (University of Connecticut) for helpful discussions. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2018",
month = sep,
day = "19",
doi = "10.1021/acs.bioconjchem.8b00484",
language = "English (US)",
volume = "29",
pages = "3161--3173",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "9",
}