| RRC ID |
39246
|
| 著者 |
Chen M, Shirai M, Liu Z, Arichi T, Takahashi H, Nishioka M.
|
| タイトル |
Efficient class II major histocompatibility complex presentation of endogenously synthesized hepatitis C virus core protein by Epstein-Barr virus-transformed B-lymphoblastoid cell lines to CD4(+) T cells.
|
| ジャーナル |
J Virol
|
| Abstract |
The induction of an efficient CD4(+) T-cell response against hepatitis C virus (HCV) is critical for control of the chronicity of HCV infection. The ability of HCV structural protein endogenously expressed in an antigen-presenting cell (APC) to be presented by class II major histocompatibility complex molecules to CD4(+) T cells was investigated by in vitro culture analyses using HCV core-specific T-cell lines and autologous Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) expressing structural HCV antigens. The T- and B-cell lines were generated from peripheral blood mononuclear cells derived from HCV-infected patients. Expression and intracellular localization of core protein in transfected cells were determined by immunoblotting and immunofluorescence. By stimulation with autologous B-LCLs expressing viral antigens, strong T-cell proliferative responses were induced in two of three patients, while no substantial stimulatory effects were produced by B-LCLs expressing a control protein (chloramphenicol acetyltransferase) or by B-LCLs alone. The results showed that transfected B cells presented mainly endogenously synthesized core peptides. Presentation of secreted antigens from adjacent antigen-expressing cells was not enough to stimulate a core-specific T-cell response. Only weak T-cell proliferative responses were generated by stimulation with B-LCLs that had been pulsed beforehand with at least a 10-fold-higher amount of transfected COS cells in the form of cell lysate, suggesting that presentation of antigens released from dead cells in the B-LCL cultures had a minimal role. Titrating numbers of APCs, we showed that as few as 10(4) transfected B-LCL APCs were sufficient to stimulate T cells. This presentation pathway was found to be leupeptin sensitive, and it can be blocked by antibody to HLA class II (DR). In addition, expression of a costimulatory signal by B7/BB1 on B cells was essential for T-cell activation.
|
| 巻・号 |
72(10)
|
| ページ |
8301-8
|
| 公開日 |
1998-10-1
|
| DOI |
10.1128/JVI.72.10.8301-8308.1998
|
| PMID |
9733874
|
| PMC |
PMC110194
|
| MeSH |
Animals
Antigen-Presenting Cells / immunology
B-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / immunology*
COS Cells
Cell Division / immunology
Cell Line, Transformed
Chloramphenicol O-Acetyltransferase / genetics
Genes, Viral
Herpesvirus 4, Human / physiology*
Histocompatibility Antigens Class II / immunology*
Leupeptins / immunology
Viral Core Proteins / immunology*
Viral Structural Proteins / genetics
|
| IF |
4.501
|
| 引用数 |
31
|
|
WOS 分野
|
VIROLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
