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ERAAP is essential for presentation of Toxoplasma gondii GRA6 protein to CD8 T cells
Author(s) -
Blanchard Nicolas,
Gonzales Federico,
Shastri Anjali,
Schaeffer Marie,
Robey Ellen A,
Shastri Nilabh
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1068.1
Subject(s) - toxoplasma gondii , antigen , cross presentation , antigen presentation , biology , antigen processing , cd8 , cytotoxic t cell , virology , mhc class i , t cell , immune system , immunology , antibody , in vitro , biochemistry
Toxoplasma gondii is an intracellular parasite that causes severe disease in immunocompromised individuals. Toxoplasma‐specific CD8 T cells confer immunity but their peptide‐MHC I ligands and the antigen processing mechanisms for Toxoplasma antigens are unknown. We generated lacZ‐inducible, Toxoplasma‐specific CD8 T cell hybridomas and used them as a probe to screen a Toxoplasma tachyzoite cDNA library. We identified GRA6, a Toxoplasma protein expressed in dense granules, as the source of a naturally processed, immunodominant, decapeptide presented by the mouse L d MHC I. Peptide/L d presentation requires active infection by tachyzoites, proteasomal activity and TAP transport. Moreover presentation by infected macrophages or dendritic cells critically depends upon expression of the ER aminopeptidase associated with antigen processing (ERAAP). Impaired presentation by ERAAP−/− antigen‐presenting cells leads to inefficient priming of GRA6‐specific CD8 T cells during infection and ERAAP‐deficient mice are susceptible to Toxoplasma infection. Thus, GRA6 is the first natural Toxoplasma antigen that elicits an immunodominant and protective CD8 T cell response. Funding by the NIH and the Human Frontier Science Program Organization