PRESENTATION OF TOXO ANTIGENS VIA THE ENDOGENOUS MHC CLASS I PATHWAY IN NON-PROFESSIONAL AND PROFESSIONAL ANTIGEN PRESENTING CELLS

Infect Immun. 2007 Sep 10; [Epub ahead of print]

PRESENTATION OF TOXOPLASMA GONDII ANTIGENS VIA THE ENDOGENOUS MHC CLASS I PATHWAY IN NON-PROFESSIONAL AND PROFESSIONAL ANTIGEN PRESENTING CELLS

Dzierszinski F, Pepper M, Stumhofer JS, Larosa DF, Wilson EH, Turka LA, Halonen SK, Hunter CA, Roos DS

Departments of Biology, Pathobiology, and Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Microbiology, Montana State University, Bozeman, MT 59717.

Challenge with the intracellular protozoan parasite Toxoplasma gondii induces a potent CD8(+) T-cell response that is required for resistance to infection, but many questions remain about the factors that regulate presentation of class I-restricted parasite antigens, and the role of professional and non-professional accessory cells. In order to address these issues, transgenic parasites expressing ovalbumin (OVA), reagents that track OVA/MHC-I presentation and OVA-specific CD8(+) T-cells were exploited to compare the ability of different infected cell types to stimulate CD8(+) T-cells and to define the factors that contribute to antigen processing. These studies reveal that a variety of infected cell types, including haematopoetic and non-haematopoetic cells, are capable of activating an OVA-specific CD8(+) T-cell hybridoma, and that this phenomenon is TAP-dependent and requires live T. gondii. Several experimental approaches indicate that T-cell activation is a consequence of direct presentation by infected host cells, rather than cross-presentation. Surprisingly, non-professional antigen presenting cells were at least as efficient as dendritic cells at activating this class I-restricted response. Studies to assess whether these cells are involved in initiation of the CD8(+) T-cell response to T. gondii in vivo show that chimeric mice expressing MHC-I only in non-haematopoietic compartments are able to activate OVA-specific CD8(+) T-cells upon challenge. These findings associate non-professional APCs with the initial activation of CD8(+) T-cells during toxoplasmosis.

PMID: 17846116 [PubMed - as supplied by publisher]