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Infect. Immun. doi:10.1128/IAI.00954-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

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

^* To whom correspondence should be addressed. Email: florence.dzierszinski{at}mcgill.ca.

	Abstract

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.