1.HBV-specific CTL responses in HLA-A2 transgenic mice induced by lipidated Th/CTL constructs
Journal of Third Military Medical University 2003;0(18):-
Objective To explore how to trigger in vivo HBV-specific HLAⅠ-restricted CTL responses to exogenously synthesized polypeptides.Methods The polypeptide was designed and synthesized based on a common helper T lymphocyte(Th) sequence of tetanus toxoid,the immunodominant CTL epitope of HBcAg and B-epitope of PreS2.The polypeptide was given to the transgenic mice respectively after being emulsified in complete or incomplete Freund's adjuvant(CFA/IFA),or inducted to 2 palmitic acid molecules(palm2-KSS,as built-in adjuvant) at its amino termini.The immunological properties of mimicing human CTL responses to HBV proteins were studied in these immunized mice.Results The HTL-CTL epitope construct with lipidated built-in adjuvant could trigger specifically and effectively vigorous in HLA-A2 transgenic mice,and dramatic difference was found compared with the mimic polypeptides emulsified in CFA and IFA(P
2.Therapeutic peptide based on CTL epitope of human melanoma antigen MART-1 can induce CD8~+ T cell response in vitro
Tongdong SHI ; Li WANG ; Zhengcai JIA ; Wei ZHOU ; Liyun ZOU ;
Journal of Third Military Medical University 2003;0(10):-
Objective To explore how to improve the immunogenicity of short epitope peptides of triggering melanoma MART 1 specific CD8 +T cell responses Methods Therapeutic peptides based on the immunodominant MART 127 35, HIV Tat49 57CCP sequence and a tetanus toxoid universal Th epitope were designed and synthesized The immunological functions were studied in PBMCs from HLA A2 + melanoma patients Results The results demonstrated that the peptides could trigger vigorous MART 1 specific CD8 + CTL activities in vitro The function of peptide containing MART 127 35 and tetanus universal Th epitope was more vigorous than that of MART 127 35 peptide, and the immunogenicty of the peptides with HIV Tat49 57CCP sequence, MART 127 35 and tetanus universal Th epitope was the most vigorous Conclusion Linkage of HIV Tat49 57CCP sequence and a tetanus universal Th epitope could dramatically improve the immunogenictiy of the MART 127 35 epitope peptide
3.Polypeptides based on CTL, T helper and B-epitopes of HBV antigens induce HLA-A2~+ human PBMCs to produce CD8~+ CTL-mediated cytotoxicity
Tongdong SHI ; Yuzhang WU ; Wei ZHOU ; Zhengcai JIA ; Liyun ZOU ;
Journal of Third Military Medical University 2002;0(12):-
Objective To explore how to trigger an HLA Ⅰ restricted CD8 + T cell response to exogenously synthesized peptides in vitro . Methods A new panel of therapeutic peptides based on the immunodominant B and CTL epitopes of HBV PreS 2 region and HBcAg and the tetanus toxoid common T helper epitopes were synthesized by Merrifield solid phase peptide synthesis, and HLA A2 + human PBMCs were used to investigate the immunological properties of the mimetic peptides. Results The results demonstrated that the peptides could trigger vigorous CD8 + HBV specific CTL responses in vitro specifically and effectively. Conclusion The results reveal that T helper plus B epitopes designing with the introduction of short and flexible linker can remarkably improve the immunogenicity of short peptides and hence produce effective CTL responses in vitro .