The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells.

Abstract

MUT1 is an H-2Kb-restricted 8-mer CTL epitope expressed in Lewis lung carcinoma (3LL) tumor cells derived from C57BL/6 (B6) mice. We constructed a chimeric gene encoding ubiquitin-fused MUT1 (pUB-MUT1). By using a gene gun, B6 mice were immunized with the gene prior to challenge with 3LL tumor cells. Tumor growth and lung metastasis were prominently suppressed in mice immunized with pUB-MUT1 but only slightly in those immunized with the MUT1 gene (pMUT) alone. CD8+ T cells were confirmed to be the final effector by in vitro experiments and in vivo removal of the cells with a corresponding antibody. Anti-tumor immunity was profoundly suppressed in mice deficient in an immuno-subunit of proteasome, LMP7. Furthermore, mice deficient in a proteasome regulator, PA28alpha/beta, failed to acquire protective immunity. Thus, application of the ubiquitin-fusion degradation pathway was useful even in immunization with genes encoding a single CTL epitope for induction of specific and active CD8+ T cells.

• Authors: Xuefeng Duan, Hajime Hisaeda, Jianying Shen, Liping Tu, Takashi Imai, Bin Chou, Shigeo Murata, Tomoki Chiba, Keiji Tanaka, Hans Jörg Fehling, Takaomi Koga, Katsuo Sueishi, Kunisuke Himeno
• Journal: International immunology (Int Immunol) Vol. 18 Issue 5 Pg. 679-87 (May 2006) ISSN: 0953-8178 [Print] England
• PMID: 16569681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• MUT 1 peptide
• Multienzyme Complexes
• Oligopeptides
• Proteins
• Ubiquitin
• Vaccines, DNA
• Interferon-gamma
• LMP7 protein
• Proteasome Endopeptidase Complex
• Psme1 protein, mouse
• Psme2 protein, mouse

Topics

• Animals
• Antigen Presentation (immunology)
• Antigen-Presenting Cells (immunology)
• Biolistics
• COS Cells
• Carcinoma, Lewis Lung (immunology, prevention & control)
• Chlorocebus aethiops
• Epitopes, T-Lymphocyte (biosynthesis, immunology)
• Female
• Interferon-gamma (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Multienzyme Complexes (deficiency, immunology)
• Oligopeptides (genetics, immunology)
• Proteasome Endopeptidase Complex (immunology, metabolism)
• Proteins (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (enzymology, immunology, metabolism)
• Tumor Cells, Cultured
• Ubiquitin (immunology, metabolism)
• Vaccines, DNA (genetics, immunology, pharmacology)