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Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells

Departments of Biology,¹ Pathobiology,² Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,³ Department of Microbiology, Montana State University, Bozeman, Montana 59717⁴

Received 12 July 2007/ Returned for modification 15 August 2007/ Accepted 30 August 2007

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 the presentation of major histocompatibility complex class I (MHC-I)-restricted parasite antigens and about the role of professional and nonprofessional 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 abilities 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 hematopoietic and nonhematopoietic cells, are capable of activating an OVA-specific CD8⁺ T-cell hybridoma, and that this phenomenon is dependent on the transporter associated with antigen processing 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, nonprofessional antigen-presenting cells (APCs) were at least as efficient as dendritic cells at activating this MHC-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 nonhematopoietic compartments are able to activate OVA-specific CD8⁺ T cells upon challenge. These findings associate nonprofessional APCs with the initial activation of CD8⁺ T cells during toxoplasmosis.

Published ahead of print on 10 September 2007.

Editor: W. A. Petri, Jr.