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The Relationship between Mojor Histocompatibility Complex Class I Molccules and Natural Killer Cells

Research Project

Project/Area Number 08670519
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionOkayama University

Principal Investigator

KIURA Katsuyuki  Okayama University Medical School.Okayama University Hospital.Assistant, 医学部附属病院, 助手 (10243502)

Co-Investigator(Kenkyū-buntansha) 田端 雅弘  岡山大学, 医学部・附属病院, 助手 (30243504)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1997: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsNatural Killer Cells / HLA Class Molecules / NK Cell Receptors / Killer Inhibitory Receptors / Negative Signal / HLA ClassI分子 / NK細胞リセプター / ClassI / Negative signal / NK細胞Receptor / GL183 / EB6 / NKB1 / Class I / NK細胞receptor / NKBI
Research Abstract

1.NK cells were purified from a homozygous donor (A2402/, B0702/, Cw0702/) using a MiniMACS separation kit, and were immunized BALB/c mice three time biweekly. 2000 clones were screened using human NK cell line NK92 (A0301/A1101, B0702/B44031, Cw0702/Cw1602) by flow cytometry. We established 17 mAbs against the common antigens between human NK cells and NY cell line. Three mAbS(4-4-24-5.4-2-44-18.4-2-44-28) were IgG1 and reacted NK cells and a small part of T cells. mAb 4-4-24-5 partially inhibited the cytotoxicity of NK92 cells against K562 cells.
2. Ly-49A is a member of the Ly-49 family of mouse NK cell receptors that inhibit cytotoxicity upon recognition of their ligands, the major histocompatibility complex (MHC) class I molecules on the target cell surface Although Ly-49A has an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail. The mechanisms underlying its inhibitory function are poorly understood. We demonstrate here that antibody-mediated co-ligation of B cell receptor (BCR) with transfected Lv-49A molecule results in abrogation of BCR-induced Interleukin-2 (IL-2) secretion and substantial reduction in activation of Erk 1/2 and p38 MAP kinases in B cell line A20. Surprisingly. BCR-induced calcium mobilization was unaffected by cross-l inking of BCR with Ly-49A.Furthermore. substitution of the single tyrosine residue in the ITIM with phenylatanine did not result in a complete loss of the inhibitory function, as measu red by BCR-induced IL-2 secretion. Deletion of the N-terminal 37 amino acid peptide which includes the ITIM did abrogate the inhibitory activity. Co-immunoprecipitation experiments revealed that, upon induction of tyrosine phosphorylation. Ly-49A rccrnits tyrosine phosphatase SHP-1 but not inositol phosphatase SHIP, and that the tyrosine residue in the ITIM is critical for this interaction. These results suggest that Ly-49A utilizes two different inhibitory mechanisms : ITIM-dependent and ITIM-independent.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] W.Zeng, K.Kiura, I.NAKAMURA et al: "Murine NK cell allospecificity-1 is defined by inhibitory ligand" The Journal of Immunology. 156. 4651-4655 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Yamane, K.Kiura, M.Tabata et al.: "Small cell lung cancer can express CD34 antigen" Anticancer Research. 17. 3627-3632 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Kiura, S.Watarai, H.Ueoka et al: "An alteration of ganglioside composition in cisplatin-resistant cell line" Anticancer Research. 18. 2957-2960 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Ueoka, K.Kiura, M.Tabata: "Arandmized trial of hybrid administration of cyclophosphamide, doxorubicine vircristine(CAV)/cisplatin and etoposide versus…" Cancer. 83. 283-290 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Moritaka, K.Kiura, H.Ueoka et al: "Cisplatin-resistant human small cell lung cancer cell line shows collateral sensitivity to vinca alkaloids" Anticancer Research. 18. 927-934 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Ueoka, M.Tabata, K.Kiura et al: "Fractionated administration of irinatecan and cisplatin for treatment of ling cancer" The British Journal of Cancer. 79(516). 984-990 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Zheng WP et al.: "Murine NK cell allospecificity-1 is defined by inhibitory ligands." J Immunol. 156. 4651-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamane H et al.: "Small cell lung cancer can express CD34 antigen." Anticancer Res. 17. 3627-32 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiura K et al.: "An alteration of ganglioside composition in cisplatin-resistant lung cancer cell line." Anticancer Res. 18. 2957-60 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueoka H et al.: "A randomized trial of hybrid administration of cyclophosphamide. doxorubicin. and vincristine (CAV) /cisplatin and etoposide (PVP) versus sequential administration of CAV-PVP for the treatment of patients with small cell lung carcinoma : results of long term follow-up." Cancer. 83. 283-90 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Moritaka T et al.: "Cisplatin-resistant human small cell lung cancer cell line shows collateral sensitivity to vinca alkaloids" Anticancer Res. 18. 927-934 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueoka H et al.: "Fractionated administration of irinotecan and cisplatin for treatment of lung cancer : a phase I study." Br J Cancer. 79 (5/6). 984-90 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] W.Zheng,K.Kiura,I.Nakamura et al: "Murine NK cell allospecificity-lis defined by inhibitory ligands" The Journal of Immunology. 156. 4651-4655 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Yamane,K.Kiura,M Tabata et al: "Small cell Lung cancer can express CD34 antigen" Anticancer Reasearch. 17. 3627-3632 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Moritaka,K.Kiura H.Ueoka et al: "Cisplatin-resistant human small cell Lung cancer cell line shows collateral sensitivity to vinca alkaloids" Anticancer Research. 18. 927-934 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Kiura,S.Watarai H.Ueoka et al: "Analteration of ganglioside composition in cisplatin-resistant Lung cancer cell line" Anticancer Research. 18. 2957-2960 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Ueoka,K.Kiura M.Tabata et al: "Arandomized trial of hybrid administration of cyclophosphamide,doxovubcine vincristine (CAV)/cisplatin and etoposide versus sequential…" Cancer. 83. 283-290 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Ueoka,M.Tabata K.Kiura et al: "Fractionated administration of irinotecan and cisplatin for treatment of lung cancer : G" British Journal of Cancer. 79(5/6). 984-990 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] W.Zheng, K.Kiura, I.Nakamura et al.: "Murine NK cell allospecificity-1 is defined by inhibitory ligands" The Journal of Immunology. 156. 4651-4655 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Matsuo, K.Kiura, H.Ueoka et al.: "Growth inhibitory Effects of antifolates an Adriamycin-vesistant human small cell lung cancer cell line" Acta Medica Okayama. 51(3). 121-127 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Yamane, K.Kiura, M.Tabata et al.: "Small cell lung cancer can express CD34 antigen" Anticancer Research. 17. 3627-3632 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Moritaka, K.Kiura, H.Ueoka et al: "Cisplatin-resistant human small cell lung cancer cell line shows collateral sensitivity to vinca alkaloids" Anticancer Research. (In Press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Hiraki, M.Tabata, H.Ueoka, K.Kiura et al.: "Direct intracerebral invasion from skull metastasis of large cell lung cancer." Internal Medicine. 36(10). 720-723 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Ueoka, K.Kiura et al.: "A randomized trial of hybrid administration of CAV/PVP varsus sequential administration of CAV-PVP for the treament of small cell lung cancer" Cancer. (In Press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] W-P Zheng,K Kiura I NAKAMURA et.al.: "Murine NK cell allospecificity-1 is defined by inhibitory ligands" The Journal of Immunology. 156. 4651-4665 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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