title: In Vitro and In Vivo Analysis of the Gram-Negative Bacteria-Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells.
abstract: Mucosal-associated invariant T (MAIT) cells recognize microbial compounds presented by the MHC-related 1 (MR1) protein. Although riboflavin precursor derivatives from Gram-positive bacteria have been characterized, some level of ligand heterogeneity has been suggested through the analysis of the MAIT cell TCR repertoire in humans and differential reactivity of human MAIT cell clones according to the bacteria. In this study, using Gram-negative bacteria mutated for the riboflavin biosynthetic pathway, we show a strict correlation between the ability to synthesize the 5-amino-ribityl-uracil riboflavin precursor and to activate polyclonal and quasi-monoclonal mouse MAIT cells. To our knowledge, we show for the first time that the semipurified bacterial fraction and the synthetic ligand activate murine MAIT cells in vitro and in vivo. We describe new MR1 ligands that do not activate MAIT cells but compete with bacterial and synthetic compounds activating MAIT cells, providing the capacity to modulate MAIT cell activation. Through competition experiments, we show that the most active synthetic MAIT cell ligand displays the same functional avidity for MR1 as does the microbial compound. Altogether, these results show that most, if not all, MAIT cell ligands found in Escherichia coli are related to the riboflavin biosynthetic pathway and display very limited heterogeneity.
authors: INSERM U932, Paris 75005, France;
authors: Claire
authors: C
authors: Soudais
authors: INSERM U932, Paris 75005, France;
authors: Fatoumata
authors: F
authors: Samassa
authors: INSERM U932, Paris 75005, France; Département de Chimie, Institut Curie, Unité Mixte de Recherche 176, Paris 75005, France;
authors: Manal
authors: M
authors: Sarkis
authors: INSERM U932, Paris 75005, France;
authors: Lionel
authors: L
authors: Le Bourhis
authors: INSERM U932, Paris 75005, France;
authors: Stéphanie
authors: S
authors: Bessoles
authors: Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Unité Mixte de Recherche 8619, Centre National de la Recherche Scientifique, Université Paris-Sud, 91405 Orsay, France;
authors: Didier
authors: D
authors: Blanot
authors: Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Unité Mixte de Recherche 8619, Centre National de la Recherche Scientifique, Université Paris-Sud, 91405 Orsay, France;
authors: Mireille
authors: M
authors: Hervé
authors: Département de Chimie, Institut Curie, Unité Mixte de Recherche 176, Paris 75005, France;
authors: Frédéric
authors: F
authors: Schmidt
authors: Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, Unité Mixte de Recherche 8619, Centre National de la Recherche Scientifique, Université Paris-Sud, 91405 Orsay, France;
authors: Dominique
authors: D
authors: Mengin-Lecreulx
authors: INSERM U932, Paris 75005, France; Département de Biologie des Tumeurs, Institut Curie, Paris 75005, France; and Centre d'Investigation Clinique, CICBT507 IGR/Curie, Paris 75005, France olivier.lantz@curie.fr.
authors: Olivier
authors: O
authors: Lantz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D066298:In Vitro Techniques; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology*; D012256:Riboflavin / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D012256:Riboflavin