Cytotoxic T lymphocyte response induced by an improved synthetic lipopeptide vaccine against cervical cancer.
OBJECTIVE
To explore cytotoxic T lymphocyte (CTL) response induced by the lipopeptide vaccine against cervical cancer.


METHODS
The immunological effect inducing CD8+ T cell-mediated cytotoxicity was investigated in human leukocyte antigen (HLA)-A2 transgenic mice and peripheral blood mononuclear cells (PBMC) of healthy HLA-A2.1+blood donor. The activity of specific CTL was measured by using a standard 4 h( 51)Cr release assay. The content of major histocompatibility complex (MHC) I on T2 cells and the expression of immune molecules on dendritic cells (DC) were detected by flow cytometry, and the concentrations of interleukin (IL)-12 and interferon-gamma were determined by ELISA.


RESULTS
The lipopeptide induced a strong epitope-specific CTL response both in vivo (transgenic mice) and in vitro (human PBMC). This CTL induction was critically dependent on the presence of the helper T lymphocyte epitope in transgenic mice, and the presence of a lipid tail bypassed the need for an adjuvant. The stability and persistence of the antigenic complex formed with the lipopeptide increased in comparison with the CTL parental peptide. The lipopeptide could induce the production of IL-12 in DC, but not the maturation of DC directly.


CONCLUSIONS
The combination of CTL and the T helper epitope and lipid molecule can remarkably improve the immunogenicity of the CTL peptide, the mechanism of which is associated with an increase in the stability and persistence of the antigenic complex formed with the lipopeptide and in the production of IL-12 in DC induced by the lipopeptide. The lipopeptide can be considered a more effective vaccine type for human being.
Xu
Dao-Hua
DH
Department of Pharmacology, Guangdong Medical College, Zhanjiang 524023, China. daohuax@yahoo.com.cn
Zhou
Chen-Hui
CH
Xia
Yong-Peng
YP
Qiu
Zong-Ying
ZY
Wu
Yu-Zhang
YZ
Jia
Zheng-Cai
ZC
Zhou
Wei
W
D000276:Adjuvants, Immunologic; D000818:Animals; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D055666:Lipopeptides / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015789:HLA-A2 Antigen; D055666:Lipopeptides; D014614:Vaccines, Synthetic; D018664:Interleukin-12