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Production of monoclonal antibody specific to HLA by utilizing HLA transgenic mice.

Research Project

Project/Area Number 01870026
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionMedical Institute of Bioreguration, Kyushu University

Principal Investigator

NISHIMURA Yasuharu  Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (10156119)

Co-Investigator(Kenkyū-buntansha) KIMURA Akinori  Department of Genetics, Medical Institute of Bioregulation, Kyushu University, R, 生体防御医学研究所, 助手 (60161551)
笹月 健彦  九州大学, 生体防御医学研究所, 教授 (50014121)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1989: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsMonoclonal antibody / Hybridoma / HLA / Allo-specificity / HLA transgenic mouse / Cell fusion / HLAアロ抗原 / HLAタイピング / ヒト主要組織適合抗原系(HLA) / HLA-DQトランスジェニックマウス
Research Abstract

The matching of HLA is very important to obtain good results in organ transplantation of bone marrow and kidney. Serological HLA typing is a well established and easy method for HLA typing. Therefore it is very important to supply enough anti-HLA antisera for HLA typing of donors and recipients in organ transplantation. But anti-HLA antisera are collected by a laborious and time consuming screening of sera from women having child and the amount of antisera was obviously limitted. In order to overcome this problem, we attempted to produce good monoclonal antibodies specific to polymorphic determinants of HLA class 11 molecules by immunizing HLA transgenic mice with human cells. For this aim, we generated HLA-DRA, DQw4 and DQw6 transgenic mice successfully. HLA molecules expressed in these transgenic mice were immunologicaly functional because 1)HLA molecules expressbd on spleen cells of trasgenic mice stimulated definite mixed lymphocyte reaction in lymph node T cells of non-transgenic mouse. 2)Transgenic mice acquired a tolerance to HLA molecules encoded for by transgene. 3)Transgenic mice acquired or lost immune responsiveness to specific soluble antigens. These transgenic mice were immunized intraperitoneally with human B lymphoblastoid cell lines expressing allogeneic HLA class 11 molecules and immune spleen cells were fused with mouse myeloma cell line P3XAg8 by standard cell fusion with polyethylene glycol. Hybridomas were selected by HAT medium and the specificity of monoclonal antibodies produced in culture supernate were determined by an investigation of binding capacity of antibodies to panel of cells utilizing ELISA and flow cytometry. Four monoclonal antibodies which distinguish DR2 subgroups were established and the frequency to obtain mabs specific to polymorphic determinants of HLA molecules seemed to be higher than the previous method in which non-transgenic mice were immunized with human cells.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (55 results)

All Other

All Publications (55 results)

  • [Publications] Fukui,Y.,Nishimura,Y.,Iwanaga,T.,Kimura,A.,Inamitsu,T.,Hanaoka,Y.,Kitagawa,T.,Sasazuki,T.: "Glycosuria and insulitis in NOD mice expressing the HLA-DQw6 molecule" J.Immunogenet.16. 445-453 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sasazuki,T.,Iwanaga,T.,Inamitsu,T.Yanagawa,Y.,Yasunami,M.,Kimura,K.,Hirokawa,K.,Nishimura,Y.: "Expression and function of human major histocompatibility complex HLA-DQw6 genes in the C57BL/6 mouse." Cold Spring Harbor Symposium on Quantitative Biology. 54. 513-520 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nishimura,Y.,Iwanaga,T.,Inamitsu,T.Yanagawa,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.,Sasazuki,T.: "Expression of human major histocompatibility complex,HLA-DQw6 genes alters the immune response in C57BL/6 mice" J.Immunol.145. 353-360 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Inamitsu,T.,Nishimura,Y.,Sasazuki,T.: "Different recognition of transgenic HLA-DQw6 molecules by mouse CD4^+ and CD8^+ T cells" Immunogenetics. 35. 46-50 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 西村 泰治: "HLAーDQトランスジェニックマウス 代謝 増刊号「免疫'89」" 中山書店, 10 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 西村 泰治: "HLA-DQトランスジェニックマウス 医学のあゆみ" 1 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 西村 泰治: "トランスジェニックマウスを用いたMHCの解析「生化学実験講座」第12巻分子免疫学、II免疫遺伝学・アレルギ-、日本生化学会編" 東京化学同人 東京, (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Fukui,Y.,Esaki,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.,Nishimura,Y.Sasazuki,T.: "HLA 1991 Vo1.II T cell repertoire and self-tolerance in the transgenic mice with HLA-DRA on Xchromosome" Oxford University Press Oxford, (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Esaki,Y.,Fukui,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K..Nishimura,Y.,Sasazuki,T.: "HLA 1991 Vol.II Functional expression of HLA-DQw4 genes in a line of transgenic C57BL/6 mouse" Oxford University Press Oxford, (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Fukui, Y., Nishimura, Y., Iwanaga, T., Kimura, A., Inamitsu, T., Hanaoka, Y., Kitagawa, T., and Sasazuki, T.: "Glycosuria and insulitis in NOD mice expressing the HLA-DQw6 molecule" J. Immunogenet. 16. 445-453 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sasazuki, T., Iwanaga, T., Inamitsu, T., Yanagawa, Y., Yasunami, M., Kimura, K., Hirokawa, K., and Nishimura, Y.: "Expression and function of human manor histocomaptibility complex HLA-DQw6 genes in the C57BL/6 mouse" Cold Spring Harbor Symposium on Quantitative Biology. 54. 513-520 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nishimura, Y., Iwanaga, T., Inamitsu, T., Yanagawa, Y., yasunami, M., Kumura, A., Hirokawa, K., and Sasazuki, T.: "Expression of human major histocompatibility complex, HLA-DQw6 genes alters the immune response in C57BL/6 mice" J. Immunol. 145. 353-360 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Inamitsu, T., Nishimura, Y., and Sasazuki, T.: "Different recognition of transgenic HLA-DQw6 molecules by mouse CD4^+ and CD8^+ T cells." Immunogenetics. 35. 46-50 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Fukunaga,M.,Yasunami,M.,Kimura,A.,Nishimura,Y.,Sasazuki,T.: "HLA-DQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." Journal of Immunology. 146. 2560-2567 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nagafuchi,S.,Kashiwagi,S.,Okada,K.,Anzai,K.,Nakamura,M.,Nishimura,Y.,Sasazuki,T.,Niho,Y.: "Reversal of non-responders and postexposure prophylaxis by intradermal hepatitis B vaccination in Japanese medical personnel." Journal of American Medical Association. 265. 2679-2683 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nishimura,Y.,Okubo,R.,Minato,S.,Itoyama,Y.,Goto,I.,Mori,M.,Hirayama,K.,Sasazuki,T.: "A possible association between HLA and HTLV-I associated myelopathy(HAM)in Japanese." Tissue Antigens. 37. 230-231 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fujisawa,K.,Kamikawaji,N.,Yasunami,M.,Kimura,A.,Nishimura,Y.,Sasazuki,T.: "High precursor frequency of human T cells reactive to HLA-DQ molecules expressed on mouse L cell transfectants." European Journal of Immunology. 21. 2341-2347 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nishimura,Y.,Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Yasunami,M.,Kimura,A.,Sasazuki,T.: "Genetic control of immune response and disease susceptibility by the HLA-DQ gene.In“The proceedings of the international symposium on Ir gene;from Biology to Medicine"" Research in Immunology. 142. 459-466 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Inamitsu,T.,Nishimura,Y.,Sasazuki,T.: "Different recognition of transgenic HLA-DQw6 molecules by mouse CD4^+ and CD8^+ T cell." Immunogenetics. 35. 46-50 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Dong,R.P.,Kimura,A.,Numano,F.,Nishimura,Y.,Sasazuki,T.: "HLA-linked susceptibility and resistance to Takayasu arteritis." Heart and Vessels,Supplement 7.

    • Related Report
      1991 Annual Research Report
  • [Publications] Dong,R.P.,Kimura,A.,Sasazuki,T.: "Sequence analysis of three noble DRw14-DRB1 alleles." Immunogenetics.

    • Related Report
      1991 Annual Research Report
  • [Publications] Dong,R.P.,Kimura,A.,Numano,F.,Yajima,M.,Hashimoto,Y.,Kishi,Y.,Nishimura,Y.,Sasazuki,T.: "HLA-DP antigen and Takayasu arteritis" Tissue Antigens.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hatae,K.,Kimura,A.,Okubo,R.,Watanabe,H.,Erlich,H.,Ueda,K.,Nishimura,Y.,Sasazuki,T.: "Genetic control of non-immune responsiveness to hepatitis B virus vaccine by an extended HLA haplotype." European Journal of Immunology.

    • Related Report
      1991 Annual Research Report
  • [Publications] 西村 泰治: "ヒトの免疫応答と疾病感受性の遺伝支配" からだの科学. 12. 149-155 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 西村 泰治: "自己免疫疾患とHLA遺伝子" 細胞工学. 10Suppl.S161-S170 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 西村 泰治、笹月 健彦: "HLA-DQによる免疫応答の制御" Medical Immunology. 21. 171-177 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 西村 泰治: "HLAの分子生物学と自己免疫疾患" 実験医学. 10. 33-39 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 西村 泰治、上川路 信博、笹月 健彦: "抗原特異的T細胞増殖反応による免疫抑制遺伝子の解析「生化学実験講座」第12巻分子免疫学II免疫遺伝学・アレルギ-、日本生化学会編" 東京化学同人東京, 6 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 西村 泰治: "トランスジェニックマウスを用いたMHCの解析「生化学実験講座」第12巻分子免疫学II免疫遺伝学・アレルギ-、日本生化学会編" 東京化学同人東京, 7 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Fukui,Y.,Esaki,Y.,Yasunami,M.,Kimura,K.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "T cell repertoire and self-tolerance in the transgenic mice with HLA-DRA on X chromosome.in “HLA 1991 Vol.II"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Esaki,Y.,Fukui,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "Functional expression of HLA-DQw4 genes in a line of transgenic C57BL/6 mouse.in“HLA 1991 Vol.II"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yoshizumi,H.,Kamikawaji,N.,Okumura,K.,Nishimura,Y.,Sasazuki,T.: "Down regulation of immune response by CD8^+ cytotoxic T cells specific to autologous antigen presenting cells.in“HLA 1991 Vol.II"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kimura,A.,Sasazuki,T.: "Organization and design of the DNA component of the 11th HLA Workshop.in“HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nishimura,Y.,Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Yasunami,M.,Kimura,A.,Sasazuki,T.: "Contribution of th HLA-DQ gene in controling immune response and disease susceptibility.In“The proceedings of the international congress on genetic intervention for diseases with unknown etiology"in“Molecular Approaches to the Study and Treatment of Human Diseases"eds T.O.Yoshida & J.M.Wilson" Elsevier Science Publisher,

    • Related Report
      1991 Annual Research Report
  • [Publications] Nishimura,Y.: "Expression of human major histocompatibility complex,HLAーDQw6 genes alters the immuneresponse in C57BL/6 mice." Journal of Immunology. 145. 353-360 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sasazuki,T.: "HLA linked immune suppression genes." Japanese Journal of Human Genetics. 35. 1-13 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ottenhoff,T.H.M.: "HLAーDQ molecules and the control of Mycobacterium Leprae specific T cell nonresponsiveness in lepromatous leprosy patients." European Journal of Immunology. 20. 2347-2350 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kamikawaji,N.: "HLAーDQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." Journal of Immunology.

    • Related Report
      1990 Annual Research Report
  • [Publications] 西村 泰治: "HLAーDQトランスジェニックマウス" 医学のあゆみ. 154. 482 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 西村 泰治: "免疫応答および疾患感受性を支配する遺伝要因" 日本体質学会雑誌. 54. 45-47 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 木村 彰方: "HLA領域遺伝子群" 肺と心. 37. 277-283 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 木村 彰方: "HLAクラスII遺伝子群" 蛋白質・核酸・酵素. 35. 3091-3103 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 木村 彰方: "MHC抗原の細胞分布" 日本臨床. 48. 551-553 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 木村 彰方: "MHC遺伝子の配置" 日本臨床. 48. 554-556 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 稲光 毅: "MHCとself peptideー免疫応答におけるself peptideの役割" 実験医学. 8. 77-80 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉住 秀之: "HLAと免疫抑制遺伝子" 日本臨床. 607. 568-573 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 稲光 毅: "トランスジェニックマウスに発現されたHLAーDQ分子の免疫学的機能に関する研究" 福岡医学雑誌. 82. 59-70 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 川原田 富朗: "HLAーDQw6遺伝子のマウス・コラ-ゲン誘導性関節炎に対する抑制効果" 福岡医学雑誌. 82. 71-85 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 西村 泰治: "Annual Review免疫1991 MHCトランスジェニックマウス" 中外医学社, 10 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 西村 泰治: "トランスジェニックマウスを用いたMHCの解析 「生化学実験講座」第12巻分子免疫学" 東京化学同人 東京, (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Nishimura: "Expression of human major histocompatibility complex,HLA-DQw6 genes alters the immune response in C57BL/6 mice"

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Fukui: "Glycosuria and insulitis in NOD mice expressing the HLA-DQw6 molecule" Journal of Immunogenetics.

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Honda: "Hashimoto thyroiditis and HLA in Japanese." Journal of Clinical Endocrinology and Metabolism. 69. 1268-1273 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Sasazuki: "“Expression and function of human major histocompatibility complex HLA-DQw6 genes in the C57BL/6 mouse"in Cold Spring Harbor Symposium on Quantitative Biology,vol 54" Cold Spring Harbor Laboratory, 10 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Sasazuki: "“Differential roles of HLA-DR and DQ in immune regulation in Progress in Immunology VII" Springer Verlag,Berlin, 7 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2019-02-15  

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