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International Immunology Advance Access originally published online on March 28, 2006
International Immunology 2006 18(5):679-687; doi:10.1093/intimm/dxl005
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Xuefeng Duan1, Hajime Hisaeda1, Jianying Shen1, Liping Tu1, Takashi Imai1, Bin Chou1, Shigeo Murata2, Tomoki Chiba2, Keiji Tanaka2, Hans Jörg Fehling3, Takaomi Koga4, Katsuo Sueishi4 and Kunisuke Himeno1

1 Department of Microbiology and Immunology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
2 Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
3 Department of Immunology, University of Ulm, Ulm, Germany
4 Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Correspondence to: K. Himeno; E-mail: himeno{at}parasite.med.kyushu-u.ac.jp

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, PA28{alpha}/ß, 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.

Keywords: antigen presentation, ubiquitin-fusion degradation pathway

Transmitting editor: T. Sasazuki


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