Photoactivable Glycolipid Antigens Generate Stable Conjugates with CD1d for Invariant Natural Killer T Cell Activation
| Autor: | Himanshu Kharkwal, Steven A. Porcelli, Judith V. Hobrath, Anne Dell, Patrick J. Moynihan, Peter J. Jervis, Gurdyal S. Besra, Liam R. Cox, Amareeta K. Besra, Simon J. North, Veemal Bhowruth, Stuart M. Haslam, Natacha Veerapen, Shalu Sharma Kharkwal, Maurice Zauderer, Padraic J. Quaid |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Antigen presentation Biomedical Engineering Pharmaceutical Science chemical and pharmacologic phenomena Bioengineering Lymphocyte Activation Article 03 medical and health sciences Immune system Glycolipid Antigen medicine Humans Antigens Pharmacology Antigen Presentation biology Chemistry Organic Chemistry carbohydrates (lipids) 030104 developmental biology medicine.anatomical_structure Biochemistry Covalent bond CD1D biology.protein Natural Killer T-Cells lipids (amino acids peptides and proteins) Antigens CD1d Glycolipids Biotechnology Conjugate |
| Zdroj: | Bioconjugate Chemistry. 29:3161-3173 |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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