Therapeutic polypeptides based on HBcAg(18-27) CTL epitope can induce antigen-specific CD(8)(+) CTL-mediated cytotoxicity in HLA-A2 transgenic mice.
OBJECTIVE
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.


CONCLUSIONS
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.
Shi
Tong-Dong
TD
Institute of Immunology, Third Military Medical University, 30 Gaotanyan Street, Chongqing 400038, China. tdshih@yahoo.com.cn
Wu
Yu-Zhang
YZ
Jia
Zheng-Cai
ZC
Zhou
Wei
W
Zou
Li-Yun
LY
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics*; D006512:Hepatitis B Core Antigens / Q000276:immunology* / Q000494:pharmacology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D016056:Immunodominant Epitopes