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

Overview

Journal ChemMedChem

Specialties Chemistry
Pharmacology

Date 2021 Apr 6

PMID 33821540

Citations 1

Authors

Roser Borras-Tuduri

Anna Alcaide

Sandrine Aspeslag

Lorena Usero

Carmen Serra

Carme Roura-Mir

Dirk Elewaut

Amadeu Llebaria

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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

Borras-Tuduri R, Alcaide A, Aspeslag S, Usero L, Serra C, Roura-Mir C ChemMedChem. 2021; 16(16):2491-2496.

PMID: 33821540 PMC: 8453509. DOI: 10.1002/cmdc.202000992.

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