The HLA-A2 restriction and immunogenicity of hepatitis C virus-spedfic cytotoxic T lymphocyte epitopes
10.3760/cma.j.issn.0254-5101.2009.09.013
- VernacularTitle:丙型肝炎病毒CTL表位的HLA-A2限制性及其免疫学效应研究
- Author:
Zhiliang DUAN
;
Lifang ZHANG
;
Qin ZHANG
;
Wenshu LI
;
Shanli ZHU
;
Jun CHEN
;
Kedong XIA
;
Jinsheng WEN
- Publication Type:Journal Article
- Keywords:
Cytotoxic T lymphocytes;
HLA-A2;
Immunogenecity
- From:
Chinese Journal of Microbiology and Immunology
2009;29(9):822-826
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the HLA-A2 restriction and immunogenicity of 5 previously identified HCV-speeific CTL epitopes. Methods Based on T2 cell, to explore the HLA-A2 restriction of previously identified HCV-specific CTL epitopes by MHC-peptide complex stabilization assay;To detect pep-tide-specific CTL in HLA-A2~+ PBMC stimulated by HLA-A2-restricted peptides by intracellular cytokine staining(ICS) and ELISPOT; To explore the cytotoxicity of peptide-specific CTL to same peptide-loaded T2 cells (target cells) by CTL cytotoxicity test. Results Among 5 previously identified CTL epitopes NS4b_78 (SMMAFSAAL) and NS5a_367 (TVSSALAEL) have high-affinity for HLA-A2 molecules(FI 1) ;ELISPOT results shown that NS4b_78(SMMAFSAAL) and NSSa_367(TVSSALAEL) induced high levels of IFN-γ-se-creting cells [(60±6) SFC/10~4 PBMC vs (4±1 ) SFC/10~4 PBMC, P < 0.01 ; (10 ± 3 ) SFC/10~4 PBMC vs (2±1 ) SFC/10~4 PBMC, P <0.01, respectively] ;ICS results indicated that there were high percentages of CD8~+ IFN-γ~+ T cells in total CD8~+T cells stimulated by these peptides [(2.33 ±0.22 ) % vs (0.05±0.01)%, P <0.001 ; (0.36±0.06)% vs (0.03±0.01)%, P <0.001, respectively]. Furthermore,peptide-specific CTL could effectively kill same peptide-loadcd T2 cells. Conclusion NS4b_78 (SMMAF-SAAL) and NSSa_367 (TVSSALAEL) were identified as HLA-A2-restricted CTL epitopes which could in-duce immune response in vitro.
