MHC I presentation of Toxoplasma gondii immunodominant antigen does not require Sec22b and is regulated by antigen orientation at the vacuole membrane
| Autor: | Néstor A. Guerrero, Emilie Bassot, Nicolas Blanchard, Jodie Lopez, Julien Santi-Rocca, Célia Buaillon, Virginie Vasseur, Sophie Blanié, Ignacio Cebrian |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CIENCIAS MÉDICAS Y DE LA SALUD Otras Ciencias Biológicas Immunology Protozoan Proteins Inmunología Ciencias de la Salud Antigens Protozoan CD8-Positive T-Lymphocytes TOXOPLASMA GONDII Epitope R-SNARE Proteins Ciencias Biológicas Mice 03 medical and health sciences Cytosol 0302 clinical medicine INTRACELLULAR PATHOGEN Antigen parasitic diseases MHC class I ANTIGEN CROSS-PRESENTATION Animals Immunology and Allergy PARASITE Antigen Presentation Host cell cytosol Salud Ocupacional biology Immunodominant Epitopes Antigen processing Intracellular parasite Histocompatibility Antigens Class I Dendritic Cells MHC restriction 3. Good health Cell biology Medicina Básica 030104 developmental biology Vacuoles biology.protein MHC I PRESENTATION Toxoplasma DENDRITIC CELL CD8 CIENCIAS NATURALES Y EXACTAS 030215 immunology |
| Popis: | 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. Fil: Buaillon, Célia. Université de Toulouse; Francia Fil: Guerrero, Néstor. Université de Toulouse; Francia Fil: Cebrián, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Université de Toulouse; Francia Fil: Blanié, Sophie. Université de Toulouse; Francia Fil: Lopez, Jodie. Université de Toulouse; Francia Fil: Bassot, Emilie. Université de Toulouse; Francia Fil: Vasseur, Virginie. Université de Toulouse; Francia Fil: Santi Rocca , Julien. Université de Toulouse; Francia Fil: Blanchard, Nicolas. Université de Toulouse; Francia |
| Databáze: | OpenAIRE |
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