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

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-gamma-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 similar to 250 H-2L(d) tetramers and to distinguish T. gondii-specific CD8(+) T cells in BALB/c mice. Results. We identified 2 T. gondii-specific H-2L(d)-restricted T cell epitopes, one from dense granule protein GRA4 and the other from rhoptry protein ROP7. H-2L(d)/GRA4 reactive T cells from multiple organ sources predominated 2 weeks after infection, while the reactivity of the H-2L(d)/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.