title: Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum.
abstract: The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8(+) T cells, but the T. gondii antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2L(d) major histocompatibility complex class I molecule. Presentation of the HF10-H-2L(d) ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8(+) T cell populations was impaired in T. gondii-infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. nicolasblanchard@berkeley.edu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.forename: Federico
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Marie
authors.initials: M
authors.lastname: Schaeffer
authors.forename: Nathalie T
authors.initials: NT
authors.lastname: Joncker
authors.forename: Tiffany
authors.initials: T
authors.lastname: Cheng
authors.forename: Anjali J
authors.initials: AJ
authors.lastname: Shastri
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Robey
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007931:Leucyl Aminopeptidase / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015800:Protozoan Proteins / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology* / Q000502:physiology; D014123:Toxoplasmosis / Q000276:immunology*; D014617:Vacuoles / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; C095047:GRA6 protein, Toxoplasma gondii; D015395:Histocompatibility Antigens Class I; D015800:Protozoan Proteins; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase