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2007 Fiscal Year Final Research Report Summary

Identification of tumor antigens by the use of human γδ TCR tetramers

Research Project

Project/Area Number 18590470
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

TANAKA Yoshimasa  Kyoto University, Graduate School of Medicine, Instructor (90280700)

Project Period (FY) 2006 – 2007
Keywordsγδ T cell / X-ray analysis / tetramer / receptor / protein / synchrocyclotron analysis / antigen recognition / refolding
Research Abstract

In the present project, the following studies were performed. (1) High resolution X-ray crystallographic analysis of γδ TCR (2) Design of γδ TCR tetramers based on the X-ray crystallographic analysis. (3) Preparation of γδ TCR tetramers. (4) Identification of tumor antigens by using γδ TCR tetramers. Regarding (1), the truncated γ-chain at 205, and δ-chain at 232 gave diffraction patterns at high resolution on preliminary X-ray analysis. By employing PEG 4000-based buffer, single crystals were obtained reproducibly, whose space group was ideal for synchrocydotron analysis. On analysis at SPring 8, diffraction patterns were obtained at the resolution limit of 1.9A, which was enough for high resolution crystallographic analysis. After molecular modeling and refinement, no contradiction was obtained for crystal structure at the resolution of up to 2.4A. In (2), a biotinylation sequence was introduced immediate downstream of δ205, which gave the most efficient refolding rate. As for (3), inclusion bodies of the original γ-chain and the biotinylated δ-chain were mixed and refolded, to which biotin was attached. Finally the biotinlated TCR was tetramerized using PE-conjugated strep〓, (4) When analyzing a wide spectrum of tumor cells by using the newly prepared tetramers, RPMI8226 was found to express ligands for the tetramers. Based on these findings, γδ T cells apparently recognize certain antigens expressed on tumor cells. In addition, IRP60 was identified as one of the molecules, which may be involved in the γδ T cell recognition of nontpeptide antigens. On analysis of various kinds of tumor cell lines, the tetramer of this molecule was found to recognize U937. In conclusion, we could take a firm stand to elucidate the mechanism for γδ T cell recognition of nonpeptide antigens.

  • Research Products

    (26 results)

All 2008 2007 2006

All Journal Article (22 results) (of which Peer Reviewed: 11 results) Presentation (2 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antbodies and T cell receptors2008

    • Author(s)
      David Y. Lin, Yoshimasa Tanaka, et. al.
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A. 105

      Pages: 3011-3016

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of Antibodies and T cell receptors2008

    • Author(s)
      David, Y., Lin, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A 105

      Pages: 3011-3016

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human γδ T cells modulate the mite allergen-specific T-helper type 2-skewed immunity2007

    • Author(s)
      Seigo Korematsu, Yoshimasa Tanaka, et. al.
    • Journal Title

      Clin. Exp. Allergy 37

      Pages: 1681-1687

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function2007

    • Author(s)
      Sigo Terawaki, Yoshimasa Tanaka, et. al.
    • Journal Title

      Int. Immununol. 19

      Pages: 881-890

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Programmed cell death 1 ligand and tumor-infiltrating CD8^+ T lymphocytes are prognostic factors of human ovarian cancer2007

    • Author(s)
      Junzo Hamanishi, Yoshimasa Tanaka, et. al.
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A. 104

      Pages: 3360-3365

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Synthesis of pyrophosphomonoester-containing compounds that stimulate vγ2vδ2 Tcells: Application to cancer immunotherapy2007

    • Author(s)
      Yoshimasa Tanaka, et. al.
    • Journal Title

      Med. Chem. 3

      Pages: 85-99

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study2007

    • Author(s)
      Hirohito Kobayashi, Yoshimasa Tanaka, et. al.
    • Journal Title

      Cancer Immunol. Immunother. 56

      Pages: 469-476

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Human γδ T cells modulate the mite allergen-specific t-helper type 2-Skewed immunity2007

    • Author(s)
      Seigo, Korematsu, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Clin. Exp. Allergy 37

      Pages: 1681-1687

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific and high-affinity binding of tetramerized PD-I.1 extracellular domain to PD-1-expressing cells : Possible application to enhance T cell function2007

    • Author(s)
      Seigo, Terawaki, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Int. Immunol 19

      Pages: 881-890

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Programmed death-1 ligand and tumor-infiltrating CD8^+ T lymphocytes are prognostic factors of human ovarian cancer2007

    • Author(s)
      Iunzo, Hamanishi, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Proc. Hatl. Acad. Sci. U.S.A 104

      Pages: 3360-3365

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthesis of pyrophosphomonoester-containing compounds that stimulate Vγ2Vδ2 T cells : Application to cancer immunotherapy2007

    • Author(s)
      Yoshimasa, Tanaka, et. al.
    • Journal Title

      Med. Chem 3

      Pages: 85-99

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma : A pilot study2007

    • Author(s)
      Hirohito, Kobayashi, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Cancer Immunol. Immunother 56

      Pages: 469-476

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structural studies of Vγ2Vδ2 T cells phophoantigens2006

    • Author(s)
      Yonghui Zhang, Yoshimasa Tanaka, et. al.
    • Journal Title

      Chemistry & Biology 13

      Pages: 985-992

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of CD166 in the activation of human γδ T cells by tumor cells sensitized with nonpeptide antigens2006

    • Author(s)
      Yu Kato, Yoshimasa Tanaka, et. al.
    • Journal Title

      J. Immunol. 177

      Pages: 877-884

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Human γδ T cells and tumor immunity2006

    • Author(s)
      Yoshimasa Tanaka
    • Journal Title

      J. Clin. Exp. Hematopathol. 46

      Pages: 11-23

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Negative regulation of activation-induced cytidine deaminase in B cells2006

    • Author(s)
      Taro Muto, Yoshimasa Tanaka
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A. 103

      Pages: 2752-2757

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Crystal structure and some properties of a major house dust allergen, Derf 22006

    • Author(s)
      Masashi Suzuki, Yoshimasa Tanaka
    • Journal Title

      Biochem. Biophys. Res. Commun. 339

      Pages: 679-686

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Structural studies of Vg2Vd2 T cells phosphoantigens2006

    • Author(s)
      Yonghul, Zhang, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Chemistry & Biology 13

      Pages: 985-992

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of CD166 in the activation of human γδ T cells by tumor cells Sensitized with nonptide antigens.2006

    • Author(s)
      Yu, Kato, Yoshimasa, Tanaka, et. al.
    • Journal Title

      J. Immunol 177

      Pages: 877-884

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Human γδ T cells and tumor immunotherapy2006

    • Author(s)
      Yoshimasa, Tanaka
    • Journal Title

      J. Clin. Exp. Med 46

      Pages: 11-23

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Negative regulation of activation-induced cytidine deaminase In B cells2006

    • Author(s)
      Taro, Muto, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A 103

      Pages: 2752-2757

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystal structure and some properties of a major house dust allergen, Derf 22006

    • Author(s)
      Masashi, Suzuki, Yoshimasa, Tanaka, et. al.
    • Journal Title

      Biochem. Biophys. Res. Commun 339

      Pages: 679-686

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ヒトγδ型T細胞の基礎と臨床応用2008

    • Author(s)
      田中義正、小林博人
    • Organizer
      第5回日本免疫治療学研究会
    • Place of Presentation
      新横浜プリンスホテル
    • Year and Date
      2008-03-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Human γδ T cells : Basic research to clinical application2008

    • Author(s)
      Yoshimasa, Tanaka, Hirohito, Kobayashi
    • Organizer
      The 5th Annual Meeting of the Japan Immunotherapy Society
    • Year and Date
      2008-03-01
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Biotherapy2006

    • Author(s)
      田中義正、小林博人
    • Total Pages
      5
    • Publisher
      癌と化学療法社
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] Multimer of extracellular domain of cell surface functional molecule2007

    • Inventor(s)
      Yoshimasa Tanaka, el. al.
    • Industrial Property Rights Holder
      京都大学小野薬品工業
    • Industrial Property Number
      PCT/JP2007/054052
    • Filing Date
      2007-03-02
    • Description
      「研究成果報告書概要(和文)」より
    • Overseas

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Published: 2010-02-04  

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