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

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Lopez, Jodie | Bittame, Amina | Massera, Céline | Vasseur, Virginie | Effantin, Grégory | Valat, Anne | Buaillon, Célia | Allart, Sophie | Fox, Barbara A | Rommereim, Leah M | Bzik, David J | Schoehn, Guy | Weissenhorn, Winfried | Dubremetz, Jean-François | Gagnon, Jean | Mercier, Corinne | Cesbron-Delauw, Marie-France | Blanchard, Nicolas

Edité par CCSD ; Elsevier Inc -

International audience. 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.

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