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1994 Fiscal Year Final Research Report Summary

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
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
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.

  • Research Products

    (16 results)

All Other

All Publications (16 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1996-04-15  

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