| Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi. | |
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MedLine Citation:
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PMID: 20059980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytotoxic CD8(+) T cells are particularly important to the development of protective immunity against the intracellular protozoan parasite, Trypanosoma cruzi, the etiological agent of Chagas disease. We have developed a new effective strategy of genetic immunization by activating CD8(+) T cells through the ubiquitin-fusion degradation (UFD) pathway. We constructed expression plasmids encoding the amastigote surface protein-2 (ASP-2) of T. cruzi. To induce the UFD pathway, a chimeric gene encoding ubiquitin fused to ASP-2 (pUB-ASP-2) was constructed. Mice immunized with pUB-ASP-2 presented lower parasitemia and longer survival period, compared with mice immunized with pASP-2 alone. Depletion of CD8(+) T cells abolished protection against T. cruzi in mice immunized with pUB-ASP-2 while depletion of CD4(+) T cells did not influence the effective immunity. Mice deficient in LMP2 or LMP7, subunits of immunoproteasomes, were not able to develop protective immunity induced. These results suggest that ubiquitin-fused antigens expressed in antigen-presenting cells were effectively degraded via the UFD pathway, and subsequently activated CD8(+) T cells. Consequently, immunization with pUB-ASP-2 was able to induce potent protective immunity against infection of T. cruzi. |
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Authors:
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Bin Chou; Kenji Hiromatsu; Hajime Hisaeda; Xuefeng Duan; Takashi Imai; Shigeo Murata; Keiji Tanaka; Kunisuke Himeno |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-07 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 392 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-17 Completed Date: 2010-03-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 277-82 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Antigens / immunology, metabolism CD8-Positive T-Lymphocytes / immunology* Chagas Disease / immunology, prevention & control* Cysteine Endopeptidases / genetics Female Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Multienzyme Complexes / genetics Neuraminidase / genetics, immunology*, metabolism Proteasome Endopeptidase Complex / genetics, metabolism* Protozoan Vaccines / genetics, immunology*, metabolism Trypanosoma cruzi / immunology* Ubiquitin / metabolism Vaccination Vaccines, DNA / genetics, immunology*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigens; 0/Multienzyme Complexes; 0/Protozoan Vaccines; 0/Ubiquitin; 0/Vaccines, DNA; 144416-78-4/LMP-2 protein; EC 3.2.1.18/ASP-2 protein, Trypanosoma cruzi; EC 3.2.1.18/Neuraminidase; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/LMP7 protein; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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