Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma

Molecular stability of the CDR3 structure of the TCRαβ gene

Hideyuki Ikeda, Noriyuki Sato, Akihiro Matsuura, Aya Sasaki, Shuji Takahashi, Daisuke Kozutsumi, Tetsuji Kobata, Ko Okumura, Yoshimasa Wada, Koichi Hirata, Kokichi Kikuchi

Research output: Contribution to journalArticle

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Abstract

In our previous study, RT-PCR suggested that cytotoxic T lymphocyte (CTL) clones may specifically recognize human autologous gastric signet ring cell tumor (HST2) by using TCR products of V(α)7 and V(β)20 subfamilies. In this report, we first determined the TCR nucleotide sequence of one such CTL clone, TcHST2. To study the clonal dominance and the TCR structural stability of HST2-specific CTL from patient's peripheral blood lymphocytes (PBL), the PBL were newly stimulated with a mixed lymphocyte-autologous tumor cell (HST2) culture (MLTC) and cytotoxic T cell lines, such as HPBL3x, were obtained. RT-PCR and the nucleotide sequence data indicated that HPBL3x also showed TCR V(α)7 and V(β)20 transcripts, and that HPBL3x TCR was composed of the exact same CDR3 gene structures as those of the TcHST2 clone. T cells with the same TCR structures were also detected in patient's non-treated peripheral blood, although they were infrequent. These data indicated that functional cytotoxic T cells with these distinct CDR3 equivalent structures were the dominant effector cells against HST2 autologous tumor cells. Moreover, the highly dominant and reproducible clonal expansion of T cells bearing heterodimeric TCR with identical variable, N diversity and constant region structures suggest that the molecular nature of governing antigenic peptide to TcHST2 may be stable and perhaps immunologically dominant in the interaction between CTL and HST2 autologous tumor cells.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalInternational Immunology
Volume8
Issue number1
DOIs
Publication statusPublished - 31-01-1996

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Cytotoxic T-Lymphocytes
Stomach
Carcinoma
T-Lymphocytes
Clone Cells
Lymphocytes
Genes
Neoplasms
Polymerase Chain Reaction
Molecular Structure
Cell Culture Techniques
Cell Line
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ikeda, Hideyuki ; Sato, Noriyuki ; Matsuura, Akihiro ; Sasaki, Aya ; Takahashi, Shuji ; Kozutsumi, Daisuke ; Kobata, Tetsuji ; Okumura, Ko ; Wada, Yoshimasa ; Hirata, Koichi ; Kikuchi, Kokichi. / Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma : Molecular stability of the CDR3 structure of the TCRαβ gene. In: International Immunology. 1996 ; Vol. 8, No. 1. pp. 75-82.
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abstract = "In our previous study, RT-PCR suggested that cytotoxic T lymphocyte (CTL) clones may specifically recognize human autologous gastric signet ring cell tumor (HST2) by using TCR products of V(α)7 and V(β)20 subfamilies. In this report, we first determined the TCR nucleotide sequence of one such CTL clone, TcHST2. To study the clonal dominance and the TCR structural stability of HST2-specific CTL from patient's peripheral blood lymphocytes (PBL), the PBL were newly stimulated with a mixed lymphocyte-autologous tumor cell (HST2) culture (MLTC) and cytotoxic T cell lines, such as HPBL3x, were obtained. RT-PCR and the nucleotide sequence data indicated that HPBL3x also showed TCR V(α)7 and V(β)20 transcripts, and that HPBL3x TCR was composed of the exact same CDR3 gene structures as those of the TcHST2 clone. T cells with the same TCR structures were also detected in patient's non-treated peripheral blood, although they were infrequent. These data indicated that functional cytotoxic T cells with these distinct CDR3 equivalent structures were the dominant effector cells against HST2 autologous tumor cells. Moreover, the highly dominant and reproducible clonal expansion of T cells bearing heterodimeric TCR with identical variable, N diversity and constant region structures suggest that the molecular nature of governing antigenic peptide to TcHST2 may be stable and perhaps immunologically dominant in the interaction between CTL and HST2 autologous tumor cells.",
author = "Hideyuki Ikeda and Noriyuki Sato and Akihiro Matsuura and Aya Sasaki and Shuji Takahashi and Daisuke Kozutsumi and Tetsuji Kobata and Ko Okumura and Yoshimasa Wada and Koichi Hirata and Kokichi Kikuchi",
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Ikeda, H, Sato, N, Matsuura, A, Sasaki, A, Takahashi, S, Kozutsumi, D, Kobata, T, Okumura, K, Wada, Y, Hirata, K & Kikuchi, K 1996, 'Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma: Molecular stability of the CDR3 structure of the TCRαβ gene', International Immunology, vol. 8, no. 1, pp. 75-82. https://doi.org/10.1093/intimm/8.1.75

Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma : Molecular stability of the CDR3 structure of the TCRαβ gene. / Ikeda, Hideyuki; Sato, Noriyuki; Matsuura, Akihiro; Sasaki, Aya; Takahashi, Shuji; Kozutsumi, Daisuke; Kobata, Tetsuji; Okumura, Ko; Wada, Yoshimasa; Hirata, Koichi; Kikuchi, Kokichi.

In: International Immunology, Vol. 8, No. 1, 31.01.1996, p. 75-82.

Research output: Contribution to journalArticle

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T1 - Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma

T2 - Molecular stability of the CDR3 structure of the TCRαβ gene

AU - Ikeda, Hideyuki

AU - Sato, Noriyuki

AU - Matsuura, Akihiro

AU - Sasaki, Aya

AU - Takahashi, Shuji

AU - Kozutsumi, Daisuke

AU - Kobata, Tetsuji

AU - Okumura, Ko

AU - Wada, Yoshimasa

AU - Hirata, Koichi

AU - Kikuchi, Kokichi

PY - 1996/1/31

Y1 - 1996/1/31

N2 - In our previous study, RT-PCR suggested that cytotoxic T lymphocyte (CTL) clones may specifically recognize human autologous gastric signet ring cell tumor (HST2) by using TCR products of V(α)7 and V(β)20 subfamilies. In this report, we first determined the TCR nucleotide sequence of one such CTL clone, TcHST2. To study the clonal dominance and the TCR structural stability of HST2-specific CTL from patient's peripheral blood lymphocytes (PBL), the PBL were newly stimulated with a mixed lymphocyte-autologous tumor cell (HST2) culture (MLTC) and cytotoxic T cell lines, such as HPBL3x, were obtained. RT-PCR and the nucleotide sequence data indicated that HPBL3x also showed TCR V(α)7 and V(β)20 transcripts, and that HPBL3x TCR was composed of the exact same CDR3 gene structures as those of the TcHST2 clone. T cells with the same TCR structures were also detected in patient's non-treated peripheral blood, although they were infrequent. These data indicated that functional cytotoxic T cells with these distinct CDR3 equivalent structures were the dominant effector cells against HST2 autologous tumor cells. Moreover, the highly dominant and reproducible clonal expansion of T cells bearing heterodimeric TCR with identical variable, N diversity and constant region structures suggest that the molecular nature of governing antigenic peptide to TcHST2 may be stable and perhaps immunologically dominant in the interaction between CTL and HST2 autologous tumor cells.

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