New Paradigm in NKT Cell Antigens : MCS-0208 (2-(Hydroxymethyl)phenylthio-phytoceramide) - an Aryl-Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells
Borràs-Tudurí, Roser (Institut de Química Avançada de Catalunya)
Alcaide, Anna (Institut de Química Avançada de Catalunya)
Aspeslag, Sandrine (Ghent University)
Usero Redrejo, Lorena (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Serra, Carmen (Institut de Química Avançada de Catalunya)
Roura Mir, Carme (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Elewaut, Dirk (Ghent University)
Llebaria, Amadeu (Institut de Química Avançada de Catalunya)

Date:	2021
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. Stimulating NKT cells. Breaking the rules of chemical structure of antigens for NKT cells stimulation, a single phenyl-hydorxymethyl moiety is able to stimulate NKT cells via CD1d presentation. The replacement of alpha-galacose by hydroxymethyl-phenyl-thioether lead to a interesting new NKT cell antigen, opening an unexplored chemical space for new antigens development with promising profile.
Grants:	Ministerio de Economía y Competitividad CTQ2014-57020-R Ministerio de Ciencia e Innovación CTQ2011-29549-C02-01 Ministerio de Educación, Cultura y Deporte FPU2013-01783 Ministerio de Educación y Ciencia AP2007-01826
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	NKT cells ; Alfa-galactosylceramide ; Aryl-ceramide ; Immunostimulation
Published in:	ChemMedChem, Vol. 16, Issue 16 (August 2021) , p. 2491-2496, ISSN 1860-7187

DOI: 10.1002/cmdc.202000992
PMID: 33821540

6 p, 2.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
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