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Anti-Nucleic Acid Antibody-Mediated Cross Presentation of An Antigen and Its CD8+ T Cell Activation
- Alternative Title
- 추옹 팜 딘
- Author(s)
- Pham, Dinh-Chuong
- Alternative Author(s)
- 추옹 팜 딘
- Advisor
- 권명희
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2013-02
- Language
- eng
- Alternative Abstract
- Cross-presentation is important for initiating cytotoxic T lymphocyte (CTL) responses against tumors. Delivery of exogenous antigens to the cross-presentation pathway in dendritic cells using a number of different carriers has been attempted to further understand the mechanisms underlying cross-presentation and to develop therapeutic tumor vaccines. The present study reports a new antigenic carrier molecule: a single chain variable region fragment (scFv) of a nucleic acid-hydrolyzing antibody, 3D8. As the CD8-T cell epitopes, chicken ovalbumin amino acid 257-264 (OVA257-264-SIINFEKL) and 250-264 (OVA250-264-SGLEQLESIINFEKL) were used for 3D8 scFv fusion partners. Purified 3D8 scFv-OVA fusion proteins with ~95% purity retained DNA-binding, DNA-hydrolyzing, cell-penetrating, and cytotoxic activity comparable to 3D8 scFv. Although 3D8-OVA proteins induced B16 and MO5 melanoma cancer cell death up to 80%, they just had little effect on the viability of DC2.4 dendritic cells. Both 3D8-OVA257-264 and 3D8-OVA250-264 showed OVA-specific CD8 T cell stimulatory effect but the activity of 3D8-OVA250-264 was higher than that of 3D8-OVA257-264. Furthermore, 3D8-OVA250-264 stimulated OVA-specific CD8 T cells through cross-presentation by dendritic cells via a proteasome dependent, brefeldin- and cycloheximide-sensitive, chloroquine- and primaquine-insensitive pathway, resulting in loading of the CTL epitope onto H-2Kb. In vivo cross-presentation and cross-priming was efficient, even without adjuvant; injection of mice with 3D8 scFv-OVA250-264 induced cross-presentation of the CTL epitope by draining lymph node CD11c+ B7.1+ MHC class IIhigh dendritic cells, elicited a CTL response, and suppressed the growth of tumors expressing the OVA epitope. This is the first report of an anti-nucleic acid antibody used to deliver exogenous antigen to the cross-presentation pathway and inhibit in vivo tumor growth.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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