Human CD8 and CD4 T cell epitopes of epithelial cancer antigens

Noriyuki Sato, Yuki Nabeta, Hiroaki Kondo, Hiroeki Sahara, Yoshihiko Hirohashi, Kiyoteru Kashiwagi, Takayuki Kanaseki, Yuriko Sato, Shunshui Rong, Itaru Hirai, Kenjiro Kamiguchi, Yasuaki Tamura, Akihiro Matsuura, Shuji Takahashi, Toshihiko Torigoe, H. Ikeda

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Recent human tumor immunology research has identified several genes coding immunogenic peptides recognized by CD8 cytotoxic T lymphocytes (CTLs) in melanoma tumors. Very recently, CD4 T cell antigenic epitopes were also determined in certain melanoma tumors. The use of these peptides in conjunction with human immunotherapy could prove to be of great benefit. However, such peptides in clinically common tumors of epithelial cell origin, such as of the stomach, colon, lung, etc., have not yet been determined extensively. We describe for the first time an HLA-A31 (A*31012)-restricted natural antigenic peptide recognized by the CD8 CTL TcHST-2 of gastric signet ring cell carcinoma cell line HST-2. We also identified the HLA-DRB1*08032-restricted peptide recognized by the CD4 T cell line TcOSC-20 of squamous cell carcinoma OSC-20 derived from the oral cavity. The antigenic peptide of HST-2, designated F4.2, is composed of 10 amino acid residues with two anchor motif residues necessary for binding to HLA-A31 molecules. The syn thetic F4.2 peptide enhanced the reactivity of TcHST-2 against HST-2 cells. Furthermore, introduction of an expression minigene coding F4.2 peptide to HLA-A31(+) cells conferred cytotoxic susceptibility to TcHST-2 on the cells. Some stomach cancer lines into which the HLA-A31 gene had been introduced, such as MKN28-A31-2, were lysed by TcHST-2, suggesting the presence of F4.2 peptide in at least some HLA-A31(+) stomach cancers. Furthermore, F4.2 peptide induced an F4.2 peptide-specific CTL response in at least 30-40% of HLA-A31(+) peripheral blood lymphocytes from gastric cancer patients, suggesting that F4.2 peptide could be used as a cancer vaccine for gastric tumors. The natural antigenic peptide of OSC-20 was also determined using acid extraction and biochemical separation and by mass spectrometry. Consequently, OSC-20 peptide was designated as the 6-1-5 peptide, an HLA-DRB1*08032-restricted 16-mer peptide with two possible anchor motifs. It has an amino acid sequence identical to that of human α-enolase, suggesting that it was derived from the processed parental α-enolase protein. We are presently attempting to determine the genes that code tumor rejection antigens recognized by HLA-A24- and A26-restricted T cells, including those of pulmonary and pancreatic carcinomas. The search for these antigenic peptides may lead to the identification of immunogenic peptide antigens that would be suitable for clinical use in commonly occurring epithelial cancers.

Original languageEnglish
JournalCancer Chemotherapy and Pharmacology
Volume46
Issue numberSUPPL.
Publication statusPublished - 25-11-2000

Fingerprint

T-Lymphocyte Epitopes
Antigens
Peptides
T-cells
Tumors
Neoplasms
Stomach Neoplasms
Cytotoxic T-Lymphocytes
HLA-DRB1 Chains
Phosphopyruvate Hydratase
Genes
Anchors
Melanoma
Stomach
HLA-A24 Antigen
Cells
Signet Ring Cell Carcinoma
Immunology
T-Lymphocytes
Amino Acids

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Sato, N., Nabeta, Y., Kondo, H., Sahara, H., Hirohashi, Y., Kashiwagi, K., ... Ikeda, H. (2000). Human CD8 and CD4 T cell epitopes of epithelial cancer antigens. Cancer Chemotherapy and Pharmacology, 46(SUPPL.).
Sato, Noriyuki ; Nabeta, Yuki ; Kondo, Hiroaki ; Sahara, Hiroeki ; Hirohashi, Yoshihiko ; Kashiwagi, Kiyoteru ; Kanaseki, Takayuki ; Sato, Yuriko ; Rong, Shunshui ; Hirai, Itaru ; Kamiguchi, Kenjiro ; Tamura, Yasuaki ; Matsuura, Akihiro ; Takahashi, Shuji ; Torigoe, Toshihiko ; Ikeda, H. / Human CD8 and CD4 T cell epitopes of epithelial cancer antigens. In: Cancer Chemotherapy and Pharmacology. 2000 ; Vol. 46, No. SUPPL.
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abstract = "Recent human tumor immunology research has identified several genes coding immunogenic peptides recognized by CD8 cytotoxic T lymphocytes (CTLs) in melanoma tumors. Very recently, CD4 T cell antigenic epitopes were also determined in certain melanoma tumors. The use of these peptides in conjunction with human immunotherapy could prove to be of great benefit. However, such peptides in clinically common tumors of epithelial cell origin, such as of the stomach, colon, lung, etc., have not yet been determined extensively. We describe for the first time an HLA-A31 (A*31012)-restricted natural antigenic peptide recognized by the CD8 CTL TcHST-2 of gastric signet ring cell carcinoma cell line HST-2. We also identified the HLA-DRB1*08032-restricted peptide recognized by the CD4 T cell line TcOSC-20 of squamous cell carcinoma OSC-20 derived from the oral cavity. The antigenic peptide of HST-2, designated F4.2, is composed of 10 amino acid residues with two anchor motif residues necessary for binding to HLA-A31 molecules. The syn thetic F4.2 peptide enhanced the reactivity of TcHST-2 against HST-2 cells. Furthermore, introduction of an expression minigene coding F4.2 peptide to HLA-A31(+) cells conferred cytotoxic susceptibility to TcHST-2 on the cells. Some stomach cancer lines into which the HLA-A31 gene had been introduced, such as MKN28-A31-2, were lysed by TcHST-2, suggesting the presence of F4.2 peptide in at least some HLA-A31(+) stomach cancers. Furthermore, F4.2 peptide induced an F4.2 peptide-specific CTL response in at least 30-40{\%} of HLA-A31(+) peripheral blood lymphocytes from gastric cancer patients, suggesting that F4.2 peptide could be used as a cancer vaccine for gastric tumors. The natural antigenic peptide of OSC-20 was also determined using acid extraction and biochemical separation and by mass spectrometry. Consequently, OSC-20 peptide was designated as the 6-1-5 peptide, an HLA-DRB1*08032-restricted 16-mer peptide with two possible anchor motifs. It has an amino acid sequence identical to that of human α-enolase, suggesting that it was derived from the processed parental α-enolase protein. We are presently attempting to determine the genes that code tumor rejection antigens recognized by HLA-A24- and A26-restricted T cells, including those of pulmonary and pancreatic carcinomas. The search for these antigenic peptides may lead to the identification of immunogenic peptide antigens that would be suitable for clinical use in commonly occurring epithelial cancers.",
author = "Noriyuki Sato and Yuki Nabeta and Hiroaki Kondo and Hiroeki Sahara and Yoshihiko Hirohashi and Kiyoteru Kashiwagi and Takayuki Kanaseki and Yuriko Sato and Shunshui Rong and Itaru Hirai and Kenjiro Kamiguchi and Yasuaki Tamura and Akihiro Matsuura and Shuji Takahashi and Toshihiko Torigoe and H. Ikeda",
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Sato, N, Nabeta, Y, Kondo, H, Sahara, H, Hirohashi, Y, Kashiwagi, K, Kanaseki, T, Sato, Y, Rong, S, Hirai, I, Kamiguchi, K, Tamura, Y, Matsuura, A, Takahashi, S, Torigoe, T & Ikeda, H 2000, 'Human CD8 and CD4 T cell epitopes of epithelial cancer antigens', Cancer Chemotherapy and Pharmacology, vol. 46, no. SUPPL..

Human CD8 and CD4 T cell epitopes of epithelial cancer antigens. / Sato, Noriyuki; Nabeta, Yuki; Kondo, Hiroaki; Sahara, Hiroeki; Hirohashi, Yoshihiko; Kashiwagi, Kiyoteru; Kanaseki, Takayuki; Sato, Yuriko; Rong, Shunshui; Hirai, Itaru; Kamiguchi, Kenjiro; Tamura, Yasuaki; Matsuura, Akihiro; Takahashi, Shuji; Torigoe, Toshihiko; Ikeda, H.

In: Cancer Chemotherapy and Pharmacology, Vol. 46, No. SUPPL., 25.11.2000.

Research output: Contribution to journalArticle

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T1 - Human CD8 and CD4 T cell epitopes of epithelial cancer antigens

AU - Sato, Noriyuki

AU - Nabeta, Yuki

AU - Kondo, Hiroaki

AU - Sahara, Hiroeki

AU - Hirohashi, Yoshihiko

AU - Kashiwagi, Kiyoteru

AU - Kanaseki, Takayuki

AU - Sato, Yuriko

AU - Rong, Shunshui

AU - Hirai, Itaru

AU - Kamiguchi, Kenjiro

AU - Tamura, Yasuaki

AU - Matsuura, Akihiro

AU - Takahashi, Shuji

AU - Torigoe, Toshihiko

AU - Ikeda, H.

PY - 2000/11/25

Y1 - 2000/11/25

N2 - Recent human tumor immunology research has identified several genes coding immunogenic peptides recognized by CD8 cytotoxic T lymphocytes (CTLs) in melanoma tumors. Very recently, CD4 T cell antigenic epitopes were also determined in certain melanoma tumors. The use of these peptides in conjunction with human immunotherapy could prove to be of great benefit. However, such peptides in clinically common tumors of epithelial cell origin, such as of the stomach, colon, lung, etc., have not yet been determined extensively. We describe for the first time an HLA-A31 (A*31012)-restricted natural antigenic peptide recognized by the CD8 CTL TcHST-2 of gastric signet ring cell carcinoma cell line HST-2. We also identified the HLA-DRB1*08032-restricted peptide recognized by the CD4 T cell line TcOSC-20 of squamous cell carcinoma OSC-20 derived from the oral cavity. The antigenic peptide of HST-2, designated F4.2, is composed of 10 amino acid residues with two anchor motif residues necessary for binding to HLA-A31 molecules. The syn thetic F4.2 peptide enhanced the reactivity of TcHST-2 against HST-2 cells. Furthermore, introduction of an expression minigene coding F4.2 peptide to HLA-A31(+) cells conferred cytotoxic susceptibility to TcHST-2 on the cells. Some stomach cancer lines into which the HLA-A31 gene had been introduced, such as MKN28-A31-2, were lysed by TcHST-2, suggesting the presence of F4.2 peptide in at least some HLA-A31(+) stomach cancers. Furthermore, F4.2 peptide induced an F4.2 peptide-specific CTL response in at least 30-40% of HLA-A31(+) peripheral blood lymphocytes from gastric cancer patients, suggesting that F4.2 peptide could be used as a cancer vaccine for gastric tumors. The natural antigenic peptide of OSC-20 was also determined using acid extraction and biochemical separation and by mass spectrometry. Consequently, OSC-20 peptide was designated as the 6-1-5 peptide, an HLA-DRB1*08032-restricted 16-mer peptide with two possible anchor motifs. It has an amino acid sequence identical to that of human α-enolase, suggesting that it was derived from the processed parental α-enolase protein. We are presently attempting to determine the genes that code tumor rejection antigens recognized by HLA-A24- and A26-restricted T cells, including those of pulmonary and pancreatic carcinomas. The search for these antigenic peptides may lead to the identification of immunogenic peptide antigens that would be suitable for clinical use in commonly occurring epithelial cancers.

AB - Recent human tumor immunology research has identified several genes coding immunogenic peptides recognized by CD8 cytotoxic T lymphocytes (CTLs) in melanoma tumors. Very recently, CD4 T cell antigenic epitopes were also determined in certain melanoma tumors. The use of these peptides in conjunction with human immunotherapy could prove to be of great benefit. However, such peptides in clinically common tumors of epithelial cell origin, such as of the stomach, colon, lung, etc., have not yet been determined extensively. We describe for the first time an HLA-A31 (A*31012)-restricted natural antigenic peptide recognized by the CD8 CTL TcHST-2 of gastric signet ring cell carcinoma cell line HST-2. We also identified the HLA-DRB1*08032-restricted peptide recognized by the CD4 T cell line TcOSC-20 of squamous cell carcinoma OSC-20 derived from the oral cavity. The antigenic peptide of HST-2, designated F4.2, is composed of 10 amino acid residues with two anchor motif residues necessary for binding to HLA-A31 molecules. The syn thetic F4.2 peptide enhanced the reactivity of TcHST-2 against HST-2 cells. Furthermore, introduction of an expression minigene coding F4.2 peptide to HLA-A31(+) cells conferred cytotoxic susceptibility to TcHST-2 on the cells. Some stomach cancer lines into which the HLA-A31 gene had been introduced, such as MKN28-A31-2, were lysed by TcHST-2, suggesting the presence of F4.2 peptide in at least some HLA-A31(+) stomach cancers. Furthermore, F4.2 peptide induced an F4.2 peptide-specific CTL response in at least 30-40% of HLA-A31(+) peripheral blood lymphocytes from gastric cancer patients, suggesting that F4.2 peptide could be used as a cancer vaccine for gastric tumors. The natural antigenic peptide of OSC-20 was also determined using acid extraction and biochemical separation and by mass spectrometry. Consequently, OSC-20 peptide was designated as the 6-1-5 peptide, an HLA-DRB1*08032-restricted 16-mer peptide with two possible anchor motifs. It has an amino acid sequence identical to that of human α-enolase, suggesting that it was derived from the processed parental α-enolase protein. We are presently attempting to determine the genes that code tumor rejection antigens recognized by HLA-A24- and A26-restricted T cells, including those of pulmonary and pancreatic carcinomas. The search for these antigenic peptides may lead to the identification of immunogenic peptide antigens that would be suitable for clinical use in commonly occurring epithelial cancers.

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Sato N, Nabeta Y, Kondo H, Sahara H, Hirohashi Y, Kashiwagi K et al. Human CD8 and CD4 T cell epitopes of epithelial cancer antigens. Cancer Chemotherapy and Pharmacology. 2000 Nov 25;46(SUPPL.).