摘要
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 of tetanus toxoid were designed and synthesized with Merrifield's solid-phase peptide synthesis method.Their immunological properties of inducing T_(H1)polarization,CD8^+ HBV-specific CTL expansion and CD8^+ T cell mediated cytotoxicity were investigated in HLA-A2 transgenic mice. RESULTS:Results demonstrated that the mimetic polypeptides comprised of the immunodominant CTL,B-, and T helper epitopes could trigger specifically and effectively vigorous 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 improve the immunogenicity of CTL epitopes in vivo.And that the mimetic therapeutic peptides based on the reasonable match of the above CTL,B- and T helper epitopes could be a promising therapeutic peptide vaccine candidate against HBV infection.
To explore how to bigger an HLAI-restricted CD8+ T cellresponse to exogenously synthesized polypeptides in vivo.
基金
Supported by the National Natural Science Foundation of China,No.30271189
the National 973 Project,No.2001CB510001
