title: T Cell Priming by Activated Nlrc5-Deficient Dendritic Cells Is Unaffected despite Partially Reduced MHC Class I Levels.
abstract: NLRC5, a member of the NOD-like receptor (NLR) protein family, has recently been characterized as the master transcriptional regulator of MHCI molecules in lymphocytes, in which it is highly expressed. However, its role in activated dendritic cells (DCs), which are instrumental to initiate T cell responses, remained elusive. We show in this study that, following stimulation of DCs with inflammatory stimuli, not only did NLRC5 level increase, but also its importance in directing MHCI transcription. Despite markedly reduced mRNA and intracellular H2-K levels, we unexpectedly observed nearly normal H2-K surface display in Nlrc5(-/-) DCs. Importantly, this discrepancy between a strong intracellular and a mild surface defect in H2-K levels was observed also in DCs with H2-K transcription defects independent of Nlrc5. Hence, alongside with demonstrating the importance of NLRC5 in MHCI transcription in activated DCs, we uncover a general mechanism counteracting low MHCI surface expression. In agreement with the decreased amount of neosynthesized MHCI, Nlrc5(-/-) DCs exhibited a defective capacity to display endogenous Ags. However, neither T cell priming by endogenous Ags nor cross-priming ability was substantially affected in activated Nlrc5(-/-) DCs. Altogether, these data show that Nlrc5 deficiency, despite significantly affecting MHCI transcription and Ag display, is not sufficient to hinder T cell activation, underlining the robustness of the T cell priming process by activated DCs.
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Giorgia
authors.initials: G
authors.lastname: Rota
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Kristina
authors.initials: K
authors.lastname: Ludigs
authors.affiliation: Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland; and.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Siegert
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Aubry
authors.initials: A
authors.lastname: Tardivel
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Leonor
authors.initials: L
authors.lastname: Morgado
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Aude
authors.initials: A
authors.lastname: De Gassart
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland; Greta.Guarda@unil.ch.
authors.forename: Greta
authors.initials: G
authors.lastname: Guarda
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C549161:NLRC5 protein, mouse