Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum

Nicolas Blanchard, Federico Gonzalez, Marie Schaeffer, Nathalie T. Joncker, Tiffany Cheng, Anjali J. Shastri, Ellen A. Robey, Nilabh Shastri

Research output: Contribution to journalArticle

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-2Ld major histocompatibility complex class I molecule. Presentation of the HF10-H-2Ld 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.

Original languageEnglish (US)
Pages (from-to)937-944
Number of pages8
JournalNature Immunology
Volume9
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Blanchard, N., Gonzalez, F., Schaeffer, M., Joncker, N. T., Cheng, T., Shastri, A. J., Robey, E. A., & Shastri, N. (2008). Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum. Nature Immunology, 9(8), 937-944. https://doi.org/10.1038/ni.1629