title: Class I major histocompatibility complex presentation of antigens that escape from the parasitophorous vacuole of Toxoplasma gondii.
abstract: The intracellular parasite Toxoplasma gondii, the causative agent of toxoplasmosis, induces a protective CD8 T-cell response in its host; however, the mechanisms by which T. gondii proteins are presented by the class I major histocompatibility complex remain largely unexplored. T. gondii resides within a specialized compartment, the parasitophorous vacuole, that sequesters the parasite and its secreted proteins from the host cell cytoplasm, suggesting that an alternative cross-priming pathway might be necessary for class I presentation of T. gondii antigens. Here we used a strain of T. gondii expressing yellow fluorescent protein and a secreted version of the model antigen ovalbumin to investigate this question. We found that presentation of ovalbumin secreted by the parasite requires the peptide transporter TAP (transporter associated with antigen processing) and occurs primarily in actively infected cells rather than bystander cells. We also found that dendritic cells are a major target of T. gondii infection in vivo and account for much of the antigen-presenting activity in the spleen. Finally, we obtained evidence that Cre protein secreted by T. gondii can mediate recombination in the nucleus of the host cell. Together, these results indicate that Toxoplasma proteins can escape from the parasitophorous vacuole into the host cytoplasm and be presented by the endogenous class I pathway, leading to direct recognition of infected cells by CD8 T cells.
authors.affiliation: Department of Molecular and Cell Biology, 471 Life Sciences Addition, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Marc-Jan
authors.initials: MJ
authors.lastname: Gubbels
authors.forename: Boris
authors.initials: B
authors.lastname: Striepen
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
authors.forename: Mustafa
authors.initials: M
authors.lastname: Turkoz
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Robey
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000469:parasitology; D005434:Flow Cytometry; D017930:Genes, Reporter; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000175:diagnosis / Q000276:immunology*; D014617:Vacuoles / Q000276:immunology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000953:Antigens, Protozoan; D015395:Histocompatibility Antigens Class I; C477327:transporter associated with antigen processing (TAP); D010047:Ovalbumin