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Regulation of Autoimmunity through synthetic peptides deduced from HLA allele-specific binding motifs.

Research Project

Project/Area Number 05454242
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionInstitute of Medical Science, St.Marianna University School of Medicine

Principal Investigator

KANEOKA Hidetoshi  M.D., D.M.S.St.Marianna University School of Medicine, Institute of Medical Science. Associate Professor, 難病治療研究センター, 助教授 (20161169)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Toshiharu  PhD.St.Marianna University School of Medicine, Institute of Medical Science. Res, 難病治療研究センター, 助手 (70247401)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsSystemic autoimmune diseases / Mixed connective tissue disease (MCTD) / U1 snRNP 70kD polypeptide / T cell epitope / HLA class II antigen / allele-specific binding motif / synthetic peptide / epitope therapy / HLAクラス11分子 / U1snRNP70kDポリペプチド / HLAクラスII分子
Research Abstract

Mixed connective tissue disease, MCTD,is one of prototypic systemic autoimmune diseases, and has a characteristic of specific autoimmune responses to snRNP,especially to 70 kD polypeptide. Human immune responses, including autoimmunity, are ignited by the presentation of epitopic peptides bound on HLA antigen binding groove to T cells. The peptides, bound to an HLA specificity, share promiscuous sequences. To establish a strategy to develop specific and harmless weapons to fight against the disease, we first analyzed the association between patients with MCTD and HLA phenotypes, and found HLA-DR2/DR4 shared epitope association with Caucasian patients with MCTD,and HLA-DR9 association with Japanese patients. Secondly, we searched sequences of HLA binding motifs within the 70kD polypeptide, found four sequences within RNA binding region of the polypeptide, and synthesized the 20mer peptides. Thirdly, those peptides were utilized for the proliferative response assay of 70kD palypeptide stimulated T cell lines from a Caucasian patient with MCTD.We demonstrate here that those peptides could modulate the autoimmune response of the patients, and show feasibility of those peptides as candidates for epitope therapy which should be disease-specific and of less adverse effects because those peptides are basically autoantigens. Lastly, we introduced peripheral blood mononucleated cells into SCID mice to establish animal models for autoimmunity to the 70kD polypeptide and for MCTD,and we successfully established the mice producing human immunoglobulins, which could also serve as tools to screen those peptides for therapeutic modulators of autoimmunity to snRNP.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Mitsuru Mochizuki: "Fine antigen specificity of humanγδT cell lines(Vγ9^+)established by repetitive stimulation with a serotype(KTH-1)of a gram-positive bacterium,Streptococcus Sanguis." European Journal of Immunology. 24(7). 1536-1543 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Charles R.Maliszewski: "The CD39 lymphoid cell activation antigen.Molecular cloning and structural characterization." Journal of Immunology. 153(8). 3574-3583 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiro Takeno: "Excessive function of peripheral blood neutrophils from patients with Behcet′s disease and from HLA-B51 transgenic mice." Arthritis and Rheumatism. 38(3). 426-433 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshiharu Nakajima: "Induction of differentiation into monocyte/macrophage cell lineage of a human eosinophilic leukemia cell line,EoL-1 by simultaneous stimulation with tumour necrosis factor-α and interferon-γ." British Journal of Haematology. 印刷中 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 坂根剛: "CD分子とリウマチ性疾患" リウマチ(日本リウマチ学会雑誌). 34(3). 664-674 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 兼岡秀俊: "自己免疫疾患,HLA." Biotherapy(日本生物学的治療学会雑誌). 8(6). 807-817 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hidetoshi Kaneoka: "Behcet′s Disease edited by B.Wechsler,P.Godeau" Excerpta Medica.Amsterdam., 714 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 兼岡秀俊: "免疫学ハイライト分子レベルの自己免疫疾患.編集,山本一彦" 中外医学社.東京, 142 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Robert W.Hoffman, et al: "Human T cell clones reactive against U small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals." Jouranl of Immunology. 151(11). 6460-6469 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuru Mochizuki, et al: "Fine antigen specificity of human gammadelta T cell lines (Vgamma9^+) established by repetitive stimulation with a serotype (KTH-1) of a gram-positive bacterium, Streptococcus Sanguis." European Journal of Immunology. 24(7). 1536-1543 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Charles R.Maliszewski, et al: "The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization." Journal of immunology. 153(8). 3574-3583 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiro Takeno, et al: "Excessive function of peripheral blood neutrophils from patients with Behcet's disease and from HLA-B51 transgenic mice." Arthritis and Rheumatism. 38(3). 426-433 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshiharu Nakajima, et al: "Induction of differentiation into monocyte/macrophage cell lineage of a human eosinophilic leukemia cell line, EoL-1 by simultaneous stimulation with tumour necrosis factor-alpha and interferon-gamma." British Journal of Haematology. (in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hidetoshi Kaneoka, et al: "Autoimmune diseases and HLA.(written in Japanese)" Biotherapy. 8(6). 807-817 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hidetoshi Kaneoka, et al: HLA-B51 involved in the hyperfunction of peripheral blood neutrophils from patients with Behcet's disease.Behcet's DIsease, edit.B.Wechsler, P.Godeau, 29-32 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hidetoshi Kaneoka, et al: Immunogenetics in autoimmune diseases. (written in Japanese) Molecular aspect of autoimmune diseases, edit.K.Yamamoto. Chugai Igakusha, Tokyo., 35-59 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuru Mochizuki: "Fine antigen specificity human γδ T cell lines(Vγ9^+)established by repetitive stimulation with a serotype(KTH-1)of a gram-positive bacterium,Streptococcus Sanguis." European Journal of Immunology. 24(7). 1536-1543. (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Charles R.Maliszewski: "The CD39 lymphoid cell activation antigen.Molecular cloning and structural characterization." Journal of.Immunology. 153(8). 3574-3583. (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mitsuhiro Takeno: "Excessive function of peripheral blood neutrophils from patients with Behcet′s disease and from HLA-B51transgenic mice." Arthritis and Rheumatism. 38(3). 426-433. (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toshiharu Nakajima: "Induction of differentiation into monocyte/macrophage cell lineage of a human eosinophilic leukemia cell line,EoL-1 by simultaneous stimulation with tumour necrosis factor-α and interferon-γ." British Journal of Haematology. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 坂根剛: "CD分子とリウマチ性疾患." リウマチ(日本リウマチ学会雑誌). 34(3). 664-674. (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 兼岡秀俊: "自己免疫疾患,HLA." Biotherapy(日本生物学的治療学会雑誌). 8(6). 807-817 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hidetoshi Kaneoka: "Behcet′s Disease edited byB.Wechsler,P.Godeau" Excerpta Medica.Amsterdam., 714 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 兼岡秀俊: "免疫学ハイライト分子レベルの自己免疫疾患.編集,山本一彦" 中外医学社.東京, 142 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Naomi Yamashita: "Effects of activin A on lgEsynthesis and cytokine production by human peripheral mononuclear cells." Clinical and Experimental Immunology. 94(1). 214-219. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 牛山理: "冷却濾過式血漿交換にて長期観察し得た悪性関節リウマチの1例." リウマチ.33(2). 149-155. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "Sweet病." 日本臨牀.本邦臨床統計集.下巻. 573-579 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "update微小循環障害、膠原病." 現代医療.25(5). 1671-1676. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "シェーグレン症候群." 耳鼻咽喉科頭頸部外科(JOHNS). 9(6). 985-992 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Robert W.Hoffman: "Human T cell clones reactive against U small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals." Journal of Immunology. 151(11). 6460-6469. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 古川浩司: "ニメスリドによるマウスII型コラーゲン関節炎抑制の作用機序." 炎症.14(1). 31-34. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mitsuru Mochizuki: "Fine specificity of human gd T cell lines(Vg^<g+>)established by repetitive stimulation-with a serotype(KTH-1)of a gram positive bacterium,Streptococcus Sanguis." European Journal of Immunology. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "日本人の混合性結合組織病(MCTD)の発症にかかわる免疫遺伝学的要因の解析." リウマチ.(印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "側頭動脈炎およびリウマチ性多発筋痛症." 臨床医.(印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "最新内科学大系.V,免疫・アレルギー疾患部門.第24巻,膠原病と類縁疾患." 中山書店, 296 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "神経疾患の遺伝学." 金原出版., 506 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mitsuhiro Takeno: "Behcet's Disease" Excerpta Medica, 714 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hidetoshi Kaneoka: "Behcet's Disease" Excerpta Medica, 714 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊,: "免疫学ブックレット,分子レベルの自己免疫疾患." 中外医学社(印刷中),

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "人類遺伝学-基礎と応用第2版." 金原出版.(印刷中),

    • Related Report
      1993 Annual Research Report
  • [Publications] 兼岡秀俊: "要介護老人ケア相談事典." 学習研究社.(印刷中),

    • Related Report
      1993 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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