title: Intravacuolar Membranes Regulate CD8 T Cell Recognition of Membrane-Bound Toxoplasma gondii Protective Antigen.
abstract: Apicomplexa parasites such as Toxoplasma gondii target effectors to and across the boundary of their parasitophorous vacuole (PV), resulting in host cell subversion and potential presentation by MHC class I molecules for CD8 T cell recognition. The host-parasite interface comprises the PV limiting membrane and a highly curved, membranous intravacuolar network (IVN) of uncertain function. Here, using a cell-free minimal system, we dissect how membrane tubules are shaped by the parasite effectors GRA2 and GRA6. We show that membrane association regulates access of the GRA6 protective antigen to the MHC I pathway in infected cells. Although insertion of GRA6 in the PV membrane is key for immunogenicity, association of GRA6 with the IVN limits presentation and curtails GRA6-specific CD8 responses in mice. Thus, membrane deformations of the PV regulate access of antigens to the MHC class I pathway, and the IVN may play a role in immune modulation.
authors.affiliation: INSERM, U1043, Toulouse 31300, France; CNRS, UMR 5282, Toulouse 31300, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, UPS, Toulouse 31300, France.
authors.forename: Jodie
authors.initials: J
authors.lastname: Lopez
authors.affiliation: CNRS, UMR 5163, Grenoble 38000, France; Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), Université Grenoble Alpes, Grenoble 38000, France.
authors.forename: Amina
authors.initials: A
authors.lastname: Bittame
authors.affiliation: CNRS, UMR 5163, Grenoble 38000, France; Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), Université Grenoble Alpes, Grenoble 38000, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Massera
authors.affiliation: INSERM, U1043, Toulouse 31300, France; CNRS, UMR 5282, Toulouse 31300, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, UPS, Toulouse 31300, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Vasseur
authors.affiliation: Institut de Biologie Structurale (IBS), Université Grenoble Alpes, Grenoble 38044, France; CNRS, IBS, Grenoble 38044, France; CEA, IBS, Grenoble 38044, France; CNRS, Unit for Virus Host-Cell Interactions (UVHCI), Grenoble 38042, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Effantin
authors.affiliation: CNRS, UMR 5163, Grenoble 38000, France; Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), Université Grenoble Alpes, Grenoble 38000, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Valat
authors.affiliation: INSERM, U1043, Toulouse 31300, France; CNRS, UMR 5282, Toulouse 31300, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, UPS, Toulouse 31300, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Buaillon
authors.affiliation: INSERM, U1043, Toulouse 31300, France; CNRS, UMR 5282, Toulouse 31300, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, UPS, Toulouse 31300, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Allart
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fox
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Rommereim
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bzik
authors.affiliation: Institut de Biologie Structurale (IBS), Université Grenoble Alpes, Grenoble 38044, France; CNRS, IBS, Grenoble 38044, France; CEA, IBS, Grenoble 38044, France; CNRS, Unit for Virus Host-Cell Interactions (UVHCI), Grenoble 38042, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Schoehn
authors.affiliation: Institut de Biologie Structurale (IBS), Université Grenoble Alpes, Grenoble 38044, France; CNRS, IBS, Grenoble 38044, France; CEA, IBS, Grenoble 38044, France; CNRS, Unit for Virus Host-Cell Interactions (UVHCI), Grenoble 38042, France.
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
authors.affiliation: CNRS, UMR 5235, Université de Montpellier, Montpellier 34000, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dubremetz
authors.affiliation: CNRS, UMR 5163, Grenoble 38000, France; Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), Université Grenoble Alpes, Grenoble 38000, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gagnon
authors.affiliation: CNRS, UMR 5163, Grenoble 38000, France; Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), Université Grenoble Alpes, Grenoble 38000, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Mercier
authors.affiliation: CNRS, UMR 5163, Grenoble 38000, France; Laboratoire Adaptation et Pathogénie des Microorganismes (LAPM), Université Grenoble Alpes, Grenoble 38000, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Cesbron-Delauw
authors.affiliation: INSERM, U1043, Toulouse 31300, France; CNRS, UMR 5282, Toulouse 31300, France; Centre de Physiopathologie de Toulouse Purpan (CPTP), Université de Toulouse, UPS, Toulouse 31300, France. Electronic address: nicolas.blanchard@inserm.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D006790:Host-Parasite Interactions / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*; D014617:Vacuoles / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; C095047:GRA6 protein, Toxoplasma gondii; C106990:Gra2 protein, Toxoplasma gondii; D015800:Protozoan Proteins