Impact of regulated secretion on antiparasitic CD8 T cell responses

Harshita Satija Grover, H. Hamlet Chu, Felice D. Kelly, Soo Jung Yang, Michael L. Reese, Nicolas Blanchard, Federico Gonzalez, Shiao Wei Chan, John C. Boothroyd, Nilabh Shastri, Ellen A. Robey

Research output: Contribution to journalArticlepeer-review

Abstract

CD8 Tcells 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 Tcell 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 Tcell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 Tcell 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 Tcell responses.

Original languageEnglish (US)
Pages (from-to)1716-1728
Number of pages13
JournalCell Reports
Volume7
Issue number5
DOIs
StatePublished - Jun 12 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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