Therapeutic polypeptides based on HBV core 18-27 epitope can induce CD8+ CTL-mediated cytotoxicity in HLA-A2+ human PBMCs.
OBJECTIVE
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.


CONCLUSIONS
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.
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
Zou
Li-Yun
LY
Zhou
Wei
W
D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D002455:Cell Division / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D015789:HLA-A2 Antigen; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D013744:Tetanus Toxin; C050807:presurface protein 2, hepatitis B surface antigen