Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes

Kazuhiro Suzuki, Hiroeki Sahara, Yohjiro Okada, Takahiro Yasoshima, Yoshihiko Hirohashi, Yuki Nabeta, Itaru Hirai, Toshihiko Torigoe, Shuji Takahashi, Akihiro Matsuura, Nobuaki Takahashi, Aya Sasaki, Manabu Suzuki, Junji Hamuro, Hideyuki Ikeda, Yoshimasa Wada, Koichi Hirata, Kokichi Kikuchi, Noriyuki Sato

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Peptides of human melanomas recognized by CD8 + CTLs have been identified, but the nature of those of nonmelanoma tumors remains to be elucidated. Previously, we established a gastric signet ring cell carcinoma HST-2 and HLA-A31 (A*31012)-restricted autologous CTL clone, TcHST.2. In the present study, we determined the natural antigenic peptides of HST-2 cells. The purified preparation of acid-extracted Ags was submitted to the peptide sequencer, and one peptide, designated F4.2 (Tyr-Ser-Trp-Met-Asp-Ile-Ser-Cys- Trp-Ile), appeared to be immunogenic. To confirm the antigenicity of F4.2 further, we constructed an expression minigene vector (pF4.2ss) coding adenovirus E3, a 19-kDa protein signal sequence plus F4.2. An introduction of pF4.2ss minigene to HST-2 and HLA-A31(+) allogeneic tumor cells clearly enhanced and induced the TcHST-2 reactivity, respectively. Furthermore, when synthetic peptides of F4.2 C-terminal-deleted peptides were pulsed to HST-2 cells, F4.2-9 (nonamers), but not F4.2-8 or F4.2-7 (octamer or heptamer, respectively), enhanced the reactivity of TcHST-2, suggesting that the N- terminal ninth Trp might be a T cell epitope. This was confirmed by lack of antigenicity when using synthetic substituted peptides as well as minigenes coding F4.2 variant peptides with Ala or Arg at the ninth position of F4.2. Meanwhile, it was indicated that the sixth position Ile was critically important for the binding to HLA-A31 molecules. Thus, our data indicate that F4.2 may work as an HLA-A31-restricted natural antigenic peptide recognized by CTLs.

Original languageEnglish
Pages (from-to)2783-2791
Number of pages9
JournalJournal of Immunology
Volume163
Issue number5
Publication statusPublished - 01-09-1999

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Signet Ring Cell Carcinoma
Cytotoxic T-Lymphocytes
Stomach
Peptides
T-Lymphocyte Epitopes
Protein Sorting Signals
Adenoviridae
HLA-A31 antigen
Melanoma
Neoplasms
Clone Cells
Acids
peptide F4.2

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Suzuki, K., Sahara, H., Okada, Y., Yasoshima, T., Hirohashi, Y., Nabeta, Y., ... Sato, N. (1999). Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes. Journal of Immunology, 163(5), 2783-2791.
Suzuki, Kazuhiro ; Sahara, Hiroeki ; Okada, Yohjiro ; Yasoshima, Takahiro ; Hirohashi, Yoshihiko ; Nabeta, Yuki ; Hirai, Itaru ; Torigoe, Toshihiko ; Takahashi, Shuji ; Matsuura, Akihiro ; Takahashi, Nobuaki ; Sasaki, Aya ; Suzuki, Manabu ; Hamuro, Junji ; Ikeda, Hideyuki ; Wada, Yoshimasa ; Hirata, Koichi ; Kikuchi, Kokichi ; Sato, Noriyuki. / Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes. In: Journal of Immunology. 1999 ; Vol. 163, No. 5. pp. 2783-2791.
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abstract = "Peptides of human melanomas recognized by CD8 + CTLs have been identified, but the nature of those of nonmelanoma tumors remains to be elucidated. Previously, we established a gastric signet ring cell carcinoma HST-2 and HLA-A31 (A*31012)-restricted autologous CTL clone, TcHST.2. In the present study, we determined the natural antigenic peptides of HST-2 cells. The purified preparation of acid-extracted Ags was submitted to the peptide sequencer, and one peptide, designated F4.2 (Tyr-Ser-Trp-Met-Asp-Ile-Ser-Cys- Trp-Ile), appeared to be immunogenic. To confirm the antigenicity of F4.2 further, we constructed an expression minigene vector (pF4.2ss) coding adenovirus E3, a 19-kDa protein signal sequence plus F4.2. An introduction of pF4.2ss minigene to HST-2 and HLA-A31(+) allogeneic tumor cells clearly enhanced and induced the TcHST-2 reactivity, respectively. Furthermore, when synthetic peptides of F4.2 C-terminal-deleted peptides were pulsed to HST-2 cells, F4.2-9 (nonamers), but not F4.2-8 or F4.2-7 (octamer or heptamer, respectively), enhanced the reactivity of TcHST-2, suggesting that the N- terminal ninth Trp might be a T cell epitope. This was confirmed by lack of antigenicity when using synthetic substituted peptides as well as minigenes coding F4.2 variant peptides with Ala or Arg at the ninth position of F4.2. Meanwhile, it was indicated that the sixth position Ile was critically important for the binding to HLA-A31 molecules. Thus, our data indicate that F4.2 may work as an HLA-A31-restricted natural antigenic peptide recognized by CTLs.",
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Suzuki, K, Sahara, H, Okada, Y, Yasoshima, T, Hirohashi, Y, Nabeta, Y, Hirai, I, Torigoe, T, Takahashi, S, Matsuura, A, Takahashi, N, Sasaki, A, Suzuki, M, Hamuro, J, Ikeda, H, Wada, Y, Hirata, K, Kikuchi, K & Sato, N 1999, 'Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes', Journal of Immunology, vol. 163, no. 5, pp. 2783-2791.

Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes. / Suzuki, Kazuhiro; Sahara, Hiroeki; Okada, Yohjiro; Yasoshima, Takahiro; Hirohashi, Yoshihiko; Nabeta, Yuki; Hirai, Itaru; Torigoe, Toshihiko; Takahashi, Shuji; Matsuura, Akihiro; Takahashi, Nobuaki; Sasaki, Aya; Suzuki, Manabu; Hamuro, Junji; Ikeda, Hideyuki; Wada, Yoshimasa; Hirata, Koichi; Kikuchi, Kokichi; Sato, Noriyuki.

In: Journal of Immunology, Vol. 163, No. 5, 01.09.1999, p. 2783-2791.

Research output: Contribution to journalArticle

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T1 - Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes

AU - Suzuki, Kazuhiro

AU - Sahara, Hiroeki

AU - Okada, Yohjiro

AU - Yasoshima, Takahiro

AU - Hirohashi, Yoshihiko

AU - Nabeta, Yuki

AU - Hirai, Itaru

AU - Torigoe, Toshihiko

AU - Takahashi, Shuji

AU - Matsuura, Akihiro

AU - Takahashi, Nobuaki

AU - Sasaki, Aya

AU - Suzuki, Manabu

AU - Hamuro, Junji

AU - Ikeda, Hideyuki

AU - Wada, Yoshimasa

AU - Hirata, Koichi

AU - Kikuchi, Kokichi

AU - Sato, Noriyuki

PY - 1999/9/1

Y1 - 1999/9/1

N2 - Peptides of human melanomas recognized by CD8 + CTLs have been identified, but the nature of those of nonmelanoma tumors remains to be elucidated. Previously, we established a gastric signet ring cell carcinoma HST-2 and HLA-A31 (A*31012)-restricted autologous CTL clone, TcHST.2. In the present study, we determined the natural antigenic peptides of HST-2 cells. The purified preparation of acid-extracted Ags was submitted to the peptide sequencer, and one peptide, designated F4.2 (Tyr-Ser-Trp-Met-Asp-Ile-Ser-Cys- Trp-Ile), appeared to be immunogenic. To confirm the antigenicity of F4.2 further, we constructed an expression minigene vector (pF4.2ss) coding adenovirus E3, a 19-kDa protein signal sequence plus F4.2. An introduction of pF4.2ss minigene to HST-2 and HLA-A31(+) allogeneic tumor cells clearly enhanced and induced the TcHST-2 reactivity, respectively. Furthermore, when synthetic peptides of F4.2 C-terminal-deleted peptides were pulsed to HST-2 cells, F4.2-9 (nonamers), but not F4.2-8 or F4.2-7 (octamer or heptamer, respectively), enhanced the reactivity of TcHST-2, suggesting that the N- terminal ninth Trp might be a T cell epitope. This was confirmed by lack of antigenicity when using synthetic substituted peptides as well as minigenes coding F4.2 variant peptides with Ala or Arg at the ninth position of F4.2. Meanwhile, it was indicated that the sixth position Ile was critically important for the binding to HLA-A31 molecules. Thus, our data indicate that F4.2 may work as an HLA-A31-restricted natural antigenic peptide recognized by CTLs.

AB - Peptides of human melanomas recognized by CD8 + CTLs have been identified, but the nature of those of nonmelanoma tumors remains to be elucidated. Previously, we established a gastric signet ring cell carcinoma HST-2 and HLA-A31 (A*31012)-restricted autologous CTL clone, TcHST.2. In the present study, we determined the natural antigenic peptides of HST-2 cells. The purified preparation of acid-extracted Ags was submitted to the peptide sequencer, and one peptide, designated F4.2 (Tyr-Ser-Trp-Met-Asp-Ile-Ser-Cys- Trp-Ile), appeared to be immunogenic. To confirm the antigenicity of F4.2 further, we constructed an expression minigene vector (pF4.2ss) coding adenovirus E3, a 19-kDa protein signal sequence plus F4.2. An introduction of pF4.2ss minigene to HST-2 and HLA-A31(+) allogeneic tumor cells clearly enhanced and induced the TcHST-2 reactivity, respectively. Furthermore, when synthetic peptides of F4.2 C-terminal-deleted peptides were pulsed to HST-2 cells, F4.2-9 (nonamers), but not F4.2-8 or F4.2-7 (octamer or heptamer, respectively), enhanced the reactivity of TcHST-2, suggesting that the N- terminal ninth Trp might be a T cell epitope. This was confirmed by lack of antigenicity when using synthetic substituted peptides as well as minigenes coding F4.2 variant peptides with Ala or Arg at the ninth position of F4.2. Meanwhile, it was indicated that the sixth position Ile was critically important for the binding to HLA-A31 molecules. Thus, our data indicate that F4.2 may work as an HLA-A31-restricted natural antigenic peptide recognized by CTLs.

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