Volume 126, Issue 10 pp. 2373-2386
Tumor Immunology

A specific cytotoxic T-lymphocyte epitope presentation system for antitumor immunity

Ying Wu

Ying Wu

State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China

The Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, China

Ying Wu and Changzhen Liu contributed equally to this work.

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Changzhen Liu

Changzhen Liu

The Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, China

Ying Wu and Changzhen Liu contributed equally to this work.

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Meiyi Sun

Meiyi Sun

Epigen Biotec, Beijing, China

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Hexiao Shen

Hexiao Shen

The Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, China

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Deyin Guo

Corresponding Author

Deyin Guo

State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China

Tel: +86-27-68752506; Fax: +86-27-68752897

Deyin Guo, Modern Virology Center, National Key Lab of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China

Bin Gao, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 1, Beichen Xilu Rd, Chaoyang District, Beijing 100101, PR China

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Bin Gao

Corresponding Author

Bin Gao

The Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, China

China-Japan Joint Laboratory for Molecular Immunology and Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, China

Tel and Fax: +86-10-64807338

Deyin Guo, Modern Virology Center, National Key Lab of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China

Bin Gao, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 1, Beichen Xilu Rd, Chaoyang District, Beijing 100101, PR China

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First published: 06 October 2009
Citations: 4

Abstract

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 (β2m). Both TAP-specific siRNA and the peptide-linked β2m 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.

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