Viral Hepatitis
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 1, 2004; 10(13): 1902-1906
Published online Jul 1, 2004. doi: 10.3748/wjg.v10.i13.1902
Therapeutic polypeptides based on HBV core 18-27 epitope can induce CD8+ CTL-mediated cytotoxicity in HLA-A2+ human PBMCs
Tong-Dong Shi, Yu-Zhang Wu, Zheng-Cai Jia, Li-Yun Zou, Wei Zhou
Tong-Dong Shi, Yu-Zhang Wu, Zheng-Cai Jia, Li-Yun Zou, Wei Zhou, Institute of Immunology, Third Military Medical University, Chongqing 400038, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No.30271189, and the National 973 Project, No.2001CB510001
Correspondence to: Dr. Tong-Dong Shi, Institute of Immunology, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China. tdshih@yahoo.com.cn
Telephone: +86-23-68752236-801 Fax: +86-23-68752789
Received: December 12, 2003
Revised: January 5, 2004
Accepted: January 12, 2004
Published online: July 1, 2004
Abstract

AIM: To explore how to improve the immunogenicity of HBcAg CTL epitope based polypeptides and to trigger an HBV-specific HLA I-restricted CD8+ T cell response in vitro.

METHODS: A new panel of mimetic therapeutic peptides based on the immunodominant B cell epitope of HBV PreS2 18-24 region, the CTL epitope of HBcAg18-27 and the universal T helper epitope of tetanus toxoid (TT) 830-843 was designed using computerized molecular design method and synthesized by Merrifield’s solid-phase peptide synthesis. Their immunological properties of stimulating activation and proliferation of lymphocytes, of inducing TH1 polarization, CD8+ T cell magnification and HBV-specific CD8+ CTL mediated cytotoxicity were investigated in vitro using HLA-A2+ human peripheral blood mononuclear cells (PBMCs) from healthy donors and chronic hepatitis B patients.

RESULTS: Results demonstrated that the therapeutic polypeptides based on immunodominant HBcAg18-27 CTL, PreS2 B- and universal TH epitopes could stimulate the activation and proliferation of lymphocytes, induce specifically and effectively CD8+ T cell expansion and vigorous HBV-specific CTL-mediated cytotoxicity in human PBMCs.

CONCLUSION: It indicated that the introduction of immunodominant T helper plus B-epitopes with short and flexible linkers could dramatically improve the immunogenicity of short CTL epitopes in vitro.

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