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New Paradigm in NKT Cell Antigens: MCS‐0208 (2‐(Hydroxymethyl)phenylthio‐phytoceramide) – an Aryl‐Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells

Natural Killer T (NKT) cells play an important role in the immune response and can be activated by glycolipids presented by CD1d protein. We present MCS‐0208, an unprecedented arylthioether‐phytoceramide able to induce potent invariant NKT (iNKT) cell activation, notably when tested in human iNKT ce...

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Detalles Bibliográficos
Autores principales: Borràs‐Tudurí, Roser, Alcaide, Anna, Aspeslag, Sandrine, Usero, Lorena, Serra, Carmen, Roura‐Mir, Carme, Elewaut, Dirk, Llebaria, Amadeu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453509/
https://www.ncbi.nlm.nih.gov/pubmed/33821540
http://dx.doi.org/10.1002/cmdc.202000992
Descripción
Sumario:Natural Killer T (NKT) cells play an important role in the immune response and can be activated by glycolipids presented by CD1d protein. We present MCS‐0208, an unprecedented arylthioether‐phytoceramide able to induce potent invariant NKT (iNKT) cell activation, notably when tested in human iNKT cells. This arylsphingolipid analog has a simple phenyl group containing a single hydroxyl substituent as a surrogate of the sugar ring. The phenylthioether structure contrasts with α‐galactosylceramide (1), the prototypical glycolipid used to induce iNKT cell stimulation, where the galactose 2’‐OH and 3’‐OH substituents are accepted as the minimal footprint and considered critical for NKT T cell receptor (TCR) recognition. A computational study supports the recognition of aromatic compound by the CD1d and TCR proteins as radically new structures for NKT cell stimulation.