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

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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.

Original languageEnglish
Pages (from-to)1103-1110
Number of pages8
JournalHuman Immunology
Volume74
Issue number9
DOIs
Publication statusPublished - 09-2013

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    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. (2013). 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. Human Immunology, 74(9), 1103-1110. https://doi.org/10.1016/j.humimm.2013.06.030