title: Impact of regulated secretion on antiparasitic CD8 T cell responses.
abstract: CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma, but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen, ROP5, that elicits a CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense-granule antigen GRA6 is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense-granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion affects the efficacy of parasite-specific CD8 T cell responses.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Harshita Satija
authors.initials: HS
authors.lastname: Grover
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: H Hamlet
authors.initials: HH
authors.lastname: Chu
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA.
authors.forename: Felice D
authors.initials: FD
authors.lastname: Kelly
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Reese
authors.affiliation: Center of Pathophysiology of Toulouse-Purpan, INSERM UMR1043-CNRS UMR5282, University of Toulouse, 31024 Toulouse Cedex 3, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Gonzalez
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Shiao Wei
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: nshastri@berkeley.edu.
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: erobey@berkeley.edu.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Robey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D055571:Secretory Pathway; D014122:Toxoplasma / Q000276:immunology / Q000378:metabolism*
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; C095047:GRA6 protein, Toxoplasma gondii; D015800:Protozoan Proteins