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In addition to supporting <jats:italic>T. gondii<\/jats:italic> growth, these proteins can be processed and presented by MHC I for CD8<jats:sup>+<\/jats:sup> T\u2010cell 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\u2010bound antigens differ in their requirement for host ER recruitment. In contrast to the soluble SAG1\u2010OVA model antigen, we find that presentation of the membrane\u2010bound 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\u2010terminal 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.<\/jats:p>","DOI":"10.1002\/eji.201646859","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T03:52:46Z","timestamp":1494906766000},"page":"1160-1170","source":"Crossref","is-referenced-by-count":26,"title":["MHC I presentation of <i>Toxoplasma gondii<\/i> immunodominant antigen does not require Sec22b and is regulated by antigen orientation at the vacuole membrane"],"prefix":"10.1002","volume":"47","author":[{"given":"C\u00e9lia","family":"Buaillon","sequence":"first","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nestor A.","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Cebrian","sequence":"additional","affiliation":[{"name":"Instituto de Histolog\u00eda y Embriolog\u00eda de Mendoza (IHEM)\u2010CONICET\/UNCuyo Facultad de Ciencias M\u00e9dicas Universidad Nacional de Cuyo  Mendoza Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Blani\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie","family":"Lopez","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Bassot","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Vasseur","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Santi\u2010Rocca","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-2161","authenticated-orcid":false,"given":"Nicolas","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie Toulouse Purpan (CPTP) INSERM CNRS Universit\u00e9 de Toulouse  UPS Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16412-X"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03648.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05135.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.140.11.3943"},{"key":"e_1_2_8_6_1","first-page":"419","article-title":"Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis","volume":"85","author":"Brown C. 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