Intravacuolar Membranes Regulate CD8 T Cell Recognition of Membrane-Bound Toxoplasma gondii Protective Antigen.

Jodie Lopez (1) , Amina Bittame (2, 3, 4) , Céline Massera (3, 2, 4) , Virginie Vasseur (1) , Grégory Effantin (5, 6, 2) , Anne Valat (3, 2) , Célia Buaillon (1) , Sophie Allart (1) , Barbara A Fox (7) , Leah M Rommereim (7) , David J Bzik (7) , Guy Schoehn (5, 6, 2) , Winfried Weissenhorn (5, 6, 2) , Jean-François Dubremetz (8) , Jean Gagnon (3, 2) , Corinne Mercier (3, 2, 4) , Marie-France Cesbron-Delauw (3, 2, 4) , Nicolas Blanchard (1)

1 CPTP - Centre de Physiopathologie Toulouse Purpan
2 UJF - Université Joseph Fourier - Grenoble 1
3 LAPM - Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble]
4 TIMC-IMAG-BNI - Barrière Naturelle et Infectiosité
5 UVHCI - Unit of Virus Host Cell Interactions = Biologie structurale des interactions entre virus et cellule hôte
6 IBS - UMR 5075 - Institut de biologie structurale
7 Department of Microbiology and Immunology
8 DIMNP - Dynamique des interactions membranaires normales et pathologiques

Apicomplexa parasites such asToxoplasma gondiitarget effectors to and across the boundary of theirparasitophorous vacuole (PV), resulting in host cellsubversion and potential presentation by MHC classI molecules for CD8 T cell recognition. The host-para-site interface comprises the PV limiting membraneand a highly curved, membranous intravacuolarnetwork (IVN) of uncertain function. Here, using acell-free minimal system, we dissect how membranetubules are shaped by the parasite effectors GRA2and GRA6. We show that membrane associationregulates access of the GRA6 protective antigen tothe MHC I pathway in infected cells. Although inser-tion of GRA6 in the PV membrane is key for immuno-genicity, association of GRA6 with the IVN limitspresentation and curtails GRA6-specific CD8 re-sponses in mice. Thus, membrane deformations ofthe PV regulate access of antigens to the MHC classI pathway, and the IVN may play a role in immunemodulation.

Domaines: Microbiologie et Parasitologie

Jodie Lopez, Amina Bittame, Céline Massera, Virginie Vasseur, Grégory Effantin, et al.. Intravacuolar Membranes Regulate CD8 T Cell Recognition of Membrane-Bound Toxoplasma gondii Protective Antigen.. Cell Reports, 2015, ⟨10.1016/j.celrep.2015.11.001⟩. ⟨hal-01240733⟩