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

J Infect Dis. 2008 Oct 15. [Epub ahead of print]

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

Frickel EM, Sahoo N, Hopp J, Gubbels MJ, Craver MP, Knoll LJ, Ploegh HL, Grotenbreg GM.

1Whitehead Institute for Biomedical Research, Cambridge, 2Department of Biology, Boston College, Chestnut Hill, Massachusetts; 3Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin.

Background. @nbsp; 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. @nbsp; We employed caged major histocompatibility complex molecules to generate 250 H-2L(d) tetramers and to distinguish T. gondii-specific CD8(+) T cells in BALB/c mice. Results. @nbsp; 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. @nbsp; 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.

PMID: 18922097 [PubMed - as supplied by publisher]