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

• Published in: Cell reports (Cambridge) 2015-12, Vol.13 (10), p.2273-2286
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Antigens, Protozoan - immunology; Blotting, Western; CD8-Positive T-Lymphocytes - immunology; Disease Models, Animal; Female; Fluorescent Antibody Technique; Host-Parasite Interactions - immunology; Life Sciences; Lymphocyte Activation - immunology; Male; Mice; Mice, Inbred C57BL; Microbiology and Parasitology; Protozoan Proteins - immunology; Toxoplasmosis - immunology; Vacuoles - immunology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.11.001

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. [Display omitted] •T. gondii GRA2 and GRA6 shape tubules of the intravacuolar network (IVN)•GRA6 association with PV membranes promotes MHC I antigen presentation•GRA6 binding to IVN limits its MHC I antigen presentation in vitro and in vivo•Membranes of T. gondii IVN may play a role in immune modulation The host-T. gondii parasite interface comprises tubular membrane deformations. Lopez et al. clarify the function of parasite GRA2 and GRA6 effectors in tubule biogenesis and report that membrane-binding properties of parasite antigens influence their MHC I presentation by infected cells, suggesting that tubules may play an immune modulatory role.