| RRC ID |
34738
|
| 著者 |
Kondo S, Demachi-Okamura A, Hirosawa T, Maki H, Fujita M, Uemura Y, Akatsuka Y, Yamamoto E, Shibata K, Ino K, Kikkawa F, Kuzushima K.
|
| タイトル |
An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules.
|
| ジャーナル |
Hum Immunol
|
| Abstract |
In an attempt to induce cytotoxic T lymphocytes (CTLs) that react to ovarian cancer cells, we isolated a CTL clone that specifically recognizes claudin-1 in an HLA-A*24:02-restricted manner. Naïve CD8(+) T lymphocytes were obtained from a healthy adult donor and stimulated twice in vitro with HLA-modified TOV21G cells that were originally derived from an ovarian clear-cell carcinoma line. The TOV21G modification involved RNAi-mediated gene silencing of intrinsic HLA molecules and lentiviral transduction of a synonymously mutated HLA-A*24:02. Then, cDNA library construction using mRNA extracted from the parental TOV21G cells and subsequent expression cloning were conducted. These experiments revealed that a CTL clone obtained from the bulk culture recognized a minimal epitope peptide RYEFGQALF, which was derived from an autoantigen claudin-1 presented by HLA-A*24:02 molecules. This clone exhibited cytolytic activities against three ovarian cancer cell lines and normal bronchial epithelial cells in an HLA-A*24:02-restricted manner. Our data indicate that HLA-modified cancer cells can be used as an artificial antigen-presenting cell to generate antigen-specific CTLs in a manner restricted by an HLA allele of interest.
|
| 巻・号 |
74(9)
|
| ページ |
1103-10
|
| 公開日 |
2013-9-1
|
| DOI |
10.1016/j.humimm.2013.06.030
|
| PII |
S0198-8859(13)00187-0
|
| PMID |
23806269
|
| MeSH |
Adenocarcinoma, Clear Cell / immunology*
Adult
Cell Line, Tumor
Claudin-1 / immunology
Claudin-1 / metabolism*
Clone Cells
Cytotoxicity, Immunologic
Epitopes, T-Lymphocyte / immunology
Epitopes, T-Lymphocyte / metabolism*
Female
HLA-A24 Antigen / genetics
HLA-A24 Antigen / metabolism*
Humans
Lymphocyte Activation
Ovarian Neoplasms / immunology*
Peptide Fragments / immunology
Peptide Fragments / metabolism*
Respiratory Mucosa / immunology
T-Lymphocytes, Cytotoxic / immunology*
Transgenes / genetics
|
| IF |
2.412
|
| 引用数 |
5
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 遺伝子材料 |
CSII-EF-MCS (RDB04378) |
