Article abstract
Nature Immunology 9, 937 - 944 (2008)
Published online: 29 June 2008 | doi:10.1038/ni.1629
Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum
Nicolas Blanchard1, Federico Gonzalez1, Marie Schaeffer1, Nathalie T Joncker1, Tiffany Cheng1, Anjali J Shastri1, Ellen A Robey1 & Nilabh Shastri1
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.
- Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Correspondence to: Nilabh Shastri1 e-mail: nshastri@berkeley.edu
Correspondence to: Nicolas Blanchard1 e-mail: nicolasblanchard@berkeley.edu
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