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Journal of Virology, May 2005, p. 5568-5576, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5568-5576.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

H-2 Kd-Restricted Hepatitis B Virus-Derived Epitope Whose Specific CD8+ T Lymphocytes Can Produce Gamma Interferon without Cytotoxicity

An Chen, Li Wang, Jingbo Zhang, Liyun Zou, Zhengcai Jia, Wei Zhou, Ying Wan, and Yuzhang Wu*

Institute of Immunology of PLA, Third Military Medical University, Chongqing, People's Republic of China

Received 9 August 2004/ Accepted 21 December 2004

It is necessary to evaluate the cytokine secretion status of CD8+ T lymphocytes and elucidate the factors influencing cytokine secretion, because the secretion of cytokines is also an important feature of CD8+ T lymphocytes, and the cytokines usually play critical roles in the outcome of diseases. We showed here that peptide AYRPPNAPI, derived from the core antigen of hepatitis B virus (HBV), could bind to H-2 Kd and induce primed splenocytes from HBcAg expression plasmid-immunized mice to produce gamma interferon (IFN-{gamma}) in H-2 Kd- and CD8-dependent manners instead of in a CD4-dependent manner. The induced cells were mainly CD3 and CD8 positive but had no cytotoxic effect on the corresponding target cells. When administered into HBV transgenic mice, these cells can decrease the serum HBV load without causing liver damage. These results suggest that this peptide is a special kind of CD8+ T-cell epitope, for which specific CD8+ T cells can produce IFN-{gamma} when antigenic stimulation is encountered but which have no cytotoxic effect on the corresponding target cells both in vitro and in HBV transgenic mice. This phenomenon indicates initially that the functional mechanisms of CD8+ T cells can be determined by their epitope specificity, which may be associated with the development of epitope-based immunotherapeutic approaches for infectious diseases and tumors.

* Corresponding author. Mailing address: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People's Republic of China. Phone: 86-23-68752680. Fax: 86-23-68752789. E-mail: yuzhangwu63{at}yahoo.com.cn.

Journal of Virology, May 2005, p. 5568-5576, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5568-5576.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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