Parasite Stage-Specific Recognition of EndogenousToxoplasma gondii-Derived CD8+ T Cell Epitopes

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Abstract

Background.

BALB/c mice control infection with the obligate intracellular parasite Toxoplasma gondii and develop a latent chronic infection in the brain, as do immunocompetent humans. Interferon-γ-producing CD8+ T cells provide essential protection against T. gondii infection, but the epitopes recognized have so far remained elusive.

Methods.

We employed caged major histocompatibility complex molecules to generate ∽ 250 H-2Ld tetramers and to distinguish T. gondii-specific CD8+ T cells in BALB/c mice.

Results.

We identified 2 T. gondii-specific H-2Ld-restricted T cell epitopes, one from dense granule protein GRA4 and the other from rhoptry protein ROP7. H-2Ld/GRA4 reactive T cells from multiple organ sources predominated 2 weeks after infection, while the reactivity of the H-2Ld/ROP7 T cells peaked 6-8 weeks after infection. BALB/c animals infected with T. gondii mutants defective in establishing a chronic infection showed altered levels of antigen-specific T cells, depending on the T. gondii mutant used.

Conclusions.

Our results shed light on the identity and the parasite stage-specificity of 2 CD8+ T cell epitopes recognized in the acute and chronic phase of infection with T. gondii.

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