Therapeutic polypeptides based on HBV core 18-27 epitope can induce CD_8~+ CTL-mediated cytotoxicity in HLA-A2~+ human PBMCs

摘要

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 T_(H1) 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 T_H 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.