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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigen Presentation / immunology
-
Antigen-Presenting Cells / immunology*
-
Biolistics
-
COS Cells
-
Carcinoma, Lewis Lung / immunology
-
Carcinoma, Lewis Lung / prevention & control
-
Chlorocebus aethiops
-
Epitopes, T-Lymphocyte / biosynthesis
-
Epitopes, T-Lymphocyte / immunology*
-
Female
-
Interferon-gamma / immunology
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Multienzyme Complexes / deficiency
-
Multienzyme Complexes / immunology
-
Oligopeptides / genetics
-
Oligopeptides / immunology*
-
Proteasome Endopeptidase Complex / immunology*
-
Proteasome Endopeptidase Complex / metabolism
-
Proteins / immunology
-
Proteins / metabolism
-
T-Lymphocytes, Cytotoxic / enzymology
-
T-Lymphocytes, Cytotoxic / immunology*
-
T-Lymphocytes, Cytotoxic / metabolism
-
Tumor Cells, Cultured
-
Ubiquitin / immunology*
-
Ubiquitin / metabolism
-
Vaccines, DNA / genetics
-
Vaccines, DNA / immunology
-
Vaccines, DNA / pharmacology
Substances
-
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