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International Immunology Advance Access published online on March 28, 2006
International Immunology, 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
Revised October 21, 2005
Accepted January 31, 2006

Article

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

Xuefeng Duan 1, Hajime Hisaeda 1, Jianying Shen 1, Liping Tu 1, Takashi Imai 1, Bin Chou 1, Shigeo Murata 2, Tomoki Chiba 2, Keiji Tanaka 2, Hans Jörg Fehling 3, Takaomi Koga 4, Katsuo Sueishi 4, and Kunisuke Himeno 1 *

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

* To whom correspondence should be addressed.
Kunisuke Himeno, E-mail: himeno{at}parasite.med.kyushu-u.ac.jp


  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, PA28{alpha}/{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.

Keywords: antigen presentation; ubiquitin-fusion degradation pathway.
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