کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2040652 | 1073122 | 2015 | 14 صفحه PDF | دانلود رایگان |

• 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
SummaryApicomplexa 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.
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Journal: - Volume 13, Issue 10, 15 December 2015, Pages 2273–2286