Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin

Munehide Nakatsugawa, Kazutaka Horie, Toshiaki Yoshikawa, Manami Shimomura, Yamato Kikuchi, Noriko Sakemura, Shiro Suzuki, Daisuke Nobuoka, Yoshihiko Hirohashi, Toshihiko Torigoe, Kenji Harada, Hideo Takasu, Noriyuki Sato, Tetsuya Nakatsura

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Lengsin is an eye lens protein with a glutamine synthetase domain. We previously identified this protein as a lung carcinoma antigen through cDNA microarray analysis. Lengsin protein is overexpressed irrespective of the histological type of lung carcinoma, but not in normal tissues other than the lens. Therefore, to significantly extend the use of Lengsin-based T-cell immunotherapies for the treatment of patients with lung carcinoma, we searched for HLA-A*0201-restricted epi-topes from this protein by screening predicted Lengsin-derived candidate peptides for the induction of tumor-reactive CTLs. Four Lengsin-derived peptides were selected by computerized algorithm based on a permissive HLA-A*0201 binding motif, and were used to immunize HLA-A*0201 transgenic (HHD) mice. Two of the immunizing peptides, Lengsin(206-215)(FIYDFCIFGV) and Lengsin(270-279)(FLPEFGISSA), induced peptide-specific cytotoxic T lymphocytes (CTLs) in HHD mice, and thus were used to stimulate human peripheral blood lymphocytes in vitro. Lengsin(206-215) and Lengsin (270-279) also induced human peptide-specific CTLs, and we were able to generate Lengsin(206-215)- and Lengsin(270-279)-specific CTL clones. The Lengsin(270-279)-specific CTL clone specifically recognized peptide-pulsed T2 cells, COS-7 cells expressing HLA-A*0201 and Lengsin, and HLA-A*0201+/Lengsin+ lung carcinoma cells in an HLA-A*0201-restricted manner. On the other hand, the Lengsin(206-215)- specific CTL clone failed to recognize HLA-A*0201+/Lengsin + target cells in the absence of cognate peptide. These results suggest that Lengsin(270-279) is naturally processed and presented by HLA-A*0201 molecules on the surface of lung carcinoma cells and may be a new target for antigen-specific T-cell immunotherapy against lung cancer.

Original languageEnglish
Pages (from-to)1041-1049
Number of pages9
JournalInternational Journal of Oncology
Volume39
Issue number4
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Fingerprint

T-Lymphocyte Epitopes
Cytotoxic T-Lymphocytes
Carcinoma
Antigens
Lung
Peptides
Clone Cells
Immunotherapy
T-Lymphocytes
Glutamate-Ammonia Ligase
Crystallins
Proteins
HLA-A*02:01 antigen
COS Cells
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Transgenic Mice
Lenses
Lung Neoplasms
Lymphocytes

Keywords

  • Cytotoxic T lymphocyte epitope
  • HLA-A*0201-restricted
  • Lengsin
  • Lung carcinoma antigen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nakatsugawa, M., Horie, K., Yoshikawa, T., Shimomura, M., Kikuchi, Y., Sakemura, N., ... Nakatsura, T. (2011). Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin. International Journal of Oncology, 39(4), 1041-1049. https://doi.org/10.3892/ijo.2011.1089

Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin. / Nakatsugawa, Munehide; Horie, Kazutaka; Yoshikawa, Toshiaki; Shimomura, Manami; Kikuchi, Yamato; Sakemura, Noriko; Suzuki, Shiro; Nobuoka, Daisuke; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Harada, Kenji; Takasu, Hideo; Sato, Noriyuki; Nakatsura, Tetsuya.

In: International Journal of Oncology, Vol. 39, No. 4, 10.2011, p. 1041-1049.

Research output: Contribution to journalArticle

Nakatsugawa, M, Horie, K, Yoshikawa, T, Shimomura, M, Kikuchi, Y, Sakemura, N, Suzuki, S, Nobuoka, D, Hirohashi, Y, Torigoe, T, Harada, K, Takasu, H, Sato, N & Nakatsura, T 2011, 'Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin', International Journal of Oncology, vol. 39, no. 4, pp. 1041-1049. https://doi.org/10.3892/ijo.2011.1089
Nakatsugawa, Munehide ; Horie, Kazutaka ; Yoshikawa, Toshiaki ; Shimomura, Manami ; Kikuchi, Yamato ; Sakemura, Noriko ; Suzuki, Shiro ; Nobuoka, Daisuke ; Hirohashi, Yoshihiko ; Torigoe, Toshihiko ; Harada, Kenji ; Takasu, Hideo ; Sato, Noriyuki ; Nakatsura, Tetsuya. / Identification of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from the lung carcinoma antigen, Lengsin. In: International Journal of Oncology. 2011 ; Vol. 39, No. 4. pp. 1041-1049.
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AU - Nobuoka, Daisuke

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