Document Detail

The involvement of immunoproteasomes in induction of MHC class I-restricted immunity targeting Toxoplasma SAG1.
MedLine Citation:
PMID:  16515877     Owner:  NLM     Status:  MEDLINE    
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.
Kazunari Ishii; Hajime Hisaeda; Xuefeng Duan; Takashi Imai; Tohru Sakai; Hans Jörg Fehling; Shigeo Murata; Tomoki Chiba; Keiji Tanaka; Shinjiro Hamano; Miyuki Sano; Akihiko Yano; Kunisuke Himeno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-18
Journal Detail:
Title:  Microbes and infection / Institut Pasteur     Volume:  8     ISSN:  1286-4579     ISO Abbreviation:  Microbes Infect.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-05-02     Completed Date:  2006-08-03     Revised Date:  2011-01-07    
Medline Journal Info:
Nlm Unique ID:  100883508     Medline TA:  Microbes Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  1045-53     Citation Subset:  IM    
Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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MeSH Terms
Antigens, Protozoan / immunology*,  metabolism
CD8-Positive T-Lymphocytes / immunology*
Histocompatibility Antigens Class I / immunology*
Immunization Schedule
Major Histocompatibility Complex / genetics,  immunology*
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Multienzyme Complexes / deficiency,  genetics,  immunology*
Proteasome Endopeptidase Complex / immunology
Proteins / genetics,  immunology
Protozoan Proteins / immunology*,  metabolism
Protozoan Vaccines / administration & dosage*
Recombinant Fusion Proteins / administration & dosage
T-Cell Antigen Receptor Specificity
Toxoplasma / immunology*
Toxoplasmosis / immunology,  prevention & control*
Ubiquitin / immunology*,  metabolism
Vaccines, DNA / administration & dosage
Reg. No./Substance:
0/Antigens, Protozoan; 0/Histocompatibility Antigens Class I; 0/Multienzyme Complexes; 0/Proteins; 0/Protozoan Proteins; 0/Protozoan Vaccines; 0/Recombinant Fusion Proteins; 0/SAG1 antigen, Toxoplasma; 0/Ubiquitin; 0/Vaccines, DNA; EC protein; EC Endopeptidase Complex; EC protein, mouse; EC protein, mouse

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