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Publication : Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to Toxoplasma gondii infection.

First Author  Tu L Year  2009
Journal  Eur J Immunol Volume  39
Issue  12 Pages  3385-94
PubMed ID  19830724 Mgi Jnum  J:155117
Mgi Id  MGI:4412319 Doi  10.1002/eji.200839117
Citation  Tu L, et al. (2009) Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to Toxoplasma gondii infection. Eur J Immunol 39(12):3385-94
abstractText  Proteasome-mediated proteolysis is responsible for the generation of immunogenic epitopes presented by MHC class I molecules, which activate antigen-specific CD8+ T cells. Immunoproteasomes, defined by the presence of the three catalytic subunits LMP2, MECL-1, and LMP7, have been hypothesized to optimize MHC class I antigen processing. In this study, we demonstrate that the infection of mice with a protozoan parasite, Toxoplasma gondii, induced the expression of LMP7 mRNA in APC and increased the capacity of APC to induce the production of IFN-gamma by antigen-specific CD8+ T cells. In vitro infection of a DC cell line with T. gondii also induced the expression of LMP7 and resulted in enhanced proteasome proteolytic activity. Finally, mice lacking LMP7 were highly susceptible to infection with T. gondii and showed a reduced number of functional CD8+ T cells. These results demonstrate that proteasomes containing LMP7 play an indispensable role in the survival of mice infected with T. gondii, presumably due to the efficient generation of CTL epitopes required for the functional development of CD8+ T cells.
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