You are here
Presentation of Toxoplasma gondii antigens via the endogenous major histocompatibility complex class I pathway in nonprofessional and professional antigen-presenting cells.
Title | Presentation of Toxoplasma gondii antigens via the endogenous major histocompatibility complex class I pathway in nonprofessional and professional antigen-presenting cells. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Dzierszinski, F, Pepper, M, Stumhofer, JS, LaRosa, DF, Wilson, EH, Turka, LA, Halonen, SK, Hunter, CA, Roos, DS |
Journal | Infect Immun |
Volume | 75 |
Issue | 11 |
Pagination | 5200-9 |
Date Published | 2007 Nov |
ISSN | 0019-9567 |
Keywords | Animals, Antigen-Presenting Cells, Antigens, Protozoan, CD8-Positive T-Lymphocytes, Female, Genes, Reporter, Histocompatibility Antigens Class I, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Toxoplasma, Toxoplasmosis |
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 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. |
DOI | 10.1128/IAI.00954-07 |
Alternate Journal | Infect. Immun. |
PubMed ID | 17846116 |
PubMed Central ID | PMC2168266 |
Grant List | AI028724 / AI / NIAID NIH HHS / United States AI062789 / AI / NIAID NIH HHS / United States AI42334 / AI / NIAID NIH HHS / United States |