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AIM:To explore how to trigger an HLAI-restricted CD8~+ T cellresponse to exogenously synthesized polypeptides in vivo.METHODS:Three mimetic therapeutic polypeptides basedon the immunodominant CTL epitope of HBcAg,the B- epitopeof HBV PreS_2 region and a common T helper sequence oftetanus toxoid were designed and synthesized withMerrifield’s solid-phase peptide synthesis method.Theirimmunological properties of inducing T_(H1)polarization,CD8~+HBV-specific CTL expansion and CD8~+ T cell mediatedcytotoxicity were investigated in HLA-A2 transgenic mice.RESULTS:Results demonstrated that the mimeticpolypeptides comprised of the immunodominant CTL,B-,and T helper epitopes could trigger specifically and effectivelyvigorous CD8~+ HBV-specific CTL-mediated cytotoxicity andT_(H1)polarization of T cells in HLA-A2 transgenic mice.CONCLUSION:A designed universal T helper plus B-epitopes with short and flexible linkers could dramaticallyimprove the immunogenicity of CTL epitopes in vivo.Andthat the mimetic therapeutic peptides based on thereasonable match of the above CTL,B- and T helper epitopescould be a promising therapeutic peptide vaccine candidateagainst HBV infection.
AIM: To explore how to trigger an HLAI-restricted CD8 ~ + T cell response to exogenously synthesized polypeptides in vivo. METHODS: Three mimetic therapeutic polypeptides based on the immunodominant CTL epitope of HBcAg, the B-epitope of HBV PreS_2 region and a common T helper sequence oftetanus toxoid were designed and synthesized with Merrifield’s solid-phase peptide synthesis. Theirimmunological properties of inducing T_ (H1) polarization, CD8 ~ + HBV-specific CTL expansion and CD8 ~ + T cell mediated cytotoxiccy were investigated in HLA- Results demonstrated that the mimeticpolypeptides comprised of the immunodominant CTL, B-, and T helper epitopes could trigger specifically and effectivelyvigorous CD8 ~ + HBV-specific CTL-mediated cytotoxicity and T_ (H1) polarization of T cells in HLA-A2 transgenic mice.CONCLUSION: A designed universal T helper plus B-epitopes with short and flexible linkers could dramatically boost the immunogenicity of CTL epitopes in vivo. Andthat the m imetic therapeutic peptide based on thereasonable match of the above CTL, B- and T helper epitopescould be a therapeutic therapeutic peptide vaccine candidate against HBV infection.