A specific cytotoxic T-lymphocyte epitope presentation system for antitumor immunity.
The magnitude of CTL-mediated immunity response is highly dependent on the density of antigenic peptide-MHC I complexes at the cell surface. In this study, we adopt a novel strategy to promote the surface level of specific peptide-MHC I complexes. The strategy combines the inhibition of transporter associated with antigen processing (TAP) with the delivery of specific peptide into endoplasmic reticulum directly without the help of TAP. First, RNA interference (RNAi) technology was used to inhibit TAP expression for blocking endogenous epitope-assembled MHC class I on cell surface. Second, a peptide epitope of interest was covalently linked onto human beta-2-microglobulin (beta2m). Both TAP-specific siRNA and the peptide-linked beta2m were delivered into antigen-presentation cells sequentially or simultaneously using a retrovirus delivery system. The combined strategy produces a significant amount of MHC I loaded with specific epitopes on the surface while reducing endogenously peptide-assembled MHC class I both in vitro and in vivo. The efficacy of induction of specific immune response with the strategy against tumor cells is demonstrated in both tumor cell lines and a syngenic graft tumor model.
Wu
Ying
Y
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
Liu
Changzhen
C
Sun
Meiyi
M
Shen
Hexiao
H
Guo
Deyin
D
Gao
Bin
B
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016086:Lentivirus; D008223:Lymphoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D000939:Epitopes; C489516:Tap2 protein, mouse