The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells.
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.
Department of Microbiology and Immunology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Xuefeng
X
Duan
Hajime
H
Hisaeda
Jianying
J
Shen
Liping
L
Tu
Takashi
T
Imai
Bin
B
Chou
Shigeo
S
Murata
Tomoki
T
Chiba
Keiji
K
Tanaka
Hans Jörg
HJ
Fehling
Takaomi
T
Koga
Katsuo
K
Sueishi
Kunisuke
K
Himeno
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D019470:Biolistics; D019556:COS Cells; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000517:prevention & control; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000172:deficiency / Q000276:immunology; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology* / Q000378:metabolism; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D018984:Epitopes, T-Lymphocyte; C096894:MUT 1 peptide; D009097:Multienzyme Complexes; D009842:Oligopeptides; D011506:Proteins; D025801:Ubiquitin; D019444:Vaccines, DNA; D007371:Interferon-gamma; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; C486213:Psme1 protein, mouse; C486214:Psme2 protein, mouse