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

Shinji Kondo, Ayako Demachi-Okamura, Tomoya Hirosawa, Hiroyuki Maki, Mitsugu Fujita, Yasushi Uemura, Yoshiki Akatsuka, Eiko Yamamoto, Kiyosumi Shibata, Kazuhiko Ino, Fumitaka Kikkawa, Kiyotaka Kuzushima

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1103-1110
ページ数8
ジャーナルHuman Immunology
74
9
DOI
出版ステータスPublished - 09-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

フィンガープリント

「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」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル