MHC I presentation of Toxoplasma gondii immunodominant antigen does not require Sec22b and is regulated by antigen orientation at the vacuole membrane. Issue 7 (8th June 2017)

• Record Type: Journal Article
• Authors: Buaillon, Célia; Guerrero, Nestor A.; Cebrian, Ignacio; Blanié, Sophie; Lopez, Jodie; Bassot, Emilie; Vasseur, Virginie; Santi‐Rocca, Julien; Blanchard, Nicolas
• Is Part Of: European journal of immunology. Volume 47:Issue 7(2017)
• Page Start: 1160
• Page End: 1170
• Publication Date: 2017-06-08
• Subjects: Antigen cross‐presentation -- Dendritic cell -- Intracellular pathogen -- MHC I presentation -- Parasite -- Toxoplasma gondii; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646859
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : MHC I presentation of vacuolar luminal versus membrane‐anchored antigens from Toxoplasma gondii have distinct requirements for host endoplasmic reticulum recruitment. The topology of antigen insertion into the vacuolar membranes determines MHC I presentation efficiency. These parameters should be taken into account for vaccine design. Abstract : The intracellular Toxoplasma gondii parasite replicates within a parasitophorous vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space, are inserted into PV membranes or are exported beyond the PV boundary. In addition to supporting T. gondii growth, these proteins can be processed and presented by MHC I for CD8 + T‐cell recognition. Yet it is unclear whether membrane binding influences the processing pathways employed and if topology of membrane antigens impacts their MHC I presentation. Here we report that the MHC I pathways of soluble and membrane‐bound antigens differ in their requirement for host ER recruitment. In contrast to the soluble SAG1‐OVA model antigen, we find that presentation of the membrane‐bound GRA6 is independent from the SNARE Sec22b, a key molecule for transfer of host endoplasmic reticulum components onto the PV. Using parasites modified to secrete a transmembrane antigen with opposite orientations, we further show that MHC I presentation is highly favored when the C‐terminal epitope is exposed to the host cell cytosol, which corresponds to GRA6 natural orientation. Our data suggest that the biochemical properties of antigens released by intracellular pathogens critically guide their processing pathway and are valuable parameters to consider for vaccination strategies.