The involvement of immunoproteasomes in induction of MHC class I-restricted immunity targeting Toxoplasma SAG1
Copyright policy )The involvement of immunoproteasomes in induction of MHC class I-restricted immunity targeting Toxoplasma SAG1
The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8+ T cells and was exploited in the development of a DNA vaccine against the intracellular protozoan Toxoplasma gondii by constructing a chimeric DNA encoding a fusion protein between murine ubiquitin and the toxoplasma antigen SAG1. The SAG1 peptide was promptly degraded in antigen-presenting cells (APCs) transfected with the chimeric DNA. Degradation, however, was hampered by incubating the APCs with the proteasome inhibitor epoxomicin. Mice vaccinated with the DNA acquired potent protective immunity mediated by MHC class I-restricted CD8+ T cells against infection by the highly virulent Toxoplasma. The accelerated degradation and induction of immunity were dependent on the UPS since mice lacking an immuno-subunit of 20S proteasome, LMP7, lost these functions, although they were independent of the proteasome regulator PA28alpha/beta complex.
- Kyushu University Japan
- University of Ulm Germany
- Institute of Medical Science Japan
- Chiba University Japan
Mice, Knockout, Protozoan Vaccines, Mice, Inbred BALB C, Proteasome Endopeptidase Complex, Recombinant Fusion Proteins, Histocompatibility Antigens Class I, Protozoan Proteins, Proteins, Antigens, Protozoan, T-Cell Antigen Receptor Specificity, Biolistics, CD8-Positive T-Lymphocytes, Major Histocompatibility Complex, Mice, Inbred C57BL, Mice, Multienzyme Complexes, Animals, Female, Toxoplasma, Immunization Schedule
Mice, Knockout, Protozoan Vaccines, Mice, Inbred BALB C, Proteasome Endopeptidase Complex, Recombinant Fusion Proteins, Histocompatibility Antigens Class I, Protozoan Proteins, Proteins, Antigens, Protozoan, T-Cell Antigen Receptor Specificity, Biolistics, CD8-Positive T-Lymphocytes, Major Histocompatibility Complex, Mice, Inbred C57BL, Mice, Multienzyme Complexes, Animals, Female, Toxoplasma, Immunization Schedule
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