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AIM:To explore how to improve the immunogenicity ofHBcAg CTL epitope based polypeptides and to trigger anHBV-specific HLA I-restricted CD8~+ T cell response in vitro.METHODS:A new panel of mimetic therapeutic peptidesbased on the immunodominant B cell epitope of HBV PreS218-24 region,the CTL epitope of HBc.Ag18-27 and theuniversal T helper epitope of tetanus toxoid (TT) 830-843was designed using computerized molecular design methodand synthesized by Merdfield’s solid-phase peptide synthesis.Their immunological properties of stimulating activation andproliferation of lymphocytes,of inducing T_(H1) polarization,CD8~+ T cell magnification and HBV-specific CD8~+ CTLmediated cytotoxicity were investigated in vitro using HLA-A2~+ human peripheral blood mononuclear cells (PBMCs) fromhealthy donors and chronic hepatitis B patients.RESULTS:Results demonstrated that the therapeuticpolypeptides based on immunodominant HBcAg18-27 CTL,PreS2 B- and universal TH epitopes could stimulate theactivation and proliferation of lymphocytes,induce specificallyand effectively CD8~+ T cell expansion and vigorous HBV-specific CTL-mediated cytotoxicity in human PBMCs.CONCLUSION:It indicated that the introduction ofimmunodominant T helper plus B-epitopes with short andflexible linkers could dramatically improve the immunogenicityof short CTL epitopes in vitro.
AIM: To explore how to improve the immunogenicity of HBcAg CTL based 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 PreS218-24 region, the CTL epitope of HBc. Ag18-27 and the universal T helper epitope of tetanus toxoid (TT) 830-843was designed using computerized molecular design method and synthesized by Merdfield’s solid-phase peptide synthesis. Their immunological properties of stimulating activation andproliferation of lymphocytes, of inducing T_ (H1) polarization, CD8 ~ + T cell magnification and HBV-specific CD8 ~ + CTLmediated cytotoxicity were investigated in vitro using HLA-A2 ~ + human peripheral blood mononuclear cells (PBMCs) from healthy donors and chronic hepatitis B patients.RESULTS: Results that that therapeuticpolypeptides based on immunodominant HBcAg18-27 CTL, PreS2 B- and universal TH epitopes could stimulate theactivation 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.