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Epitope specific immunotherapy for myasthenia gravis using a complementary peptide.

Research Project

Project/Area Number 09670657
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTottori University

Principal Investigator

ARAGA Shigeru  Faculty of Medicine, TOTTORI UNIVERSITY, Associate Professor., 医学部, 助教授 (40193065)

Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsANTI-IDIOTYPE ANTIBODIES / IDIOTYPE ANTIBODIES / COMPLEMENTARY PEPTIDE / MYASTHENIA GRAVIS / pGEM VECTOR / PiPoin Xa-1 VECTOR / Pin Point Xa-1 vector / 相補性ペプチド
Research Abstract

We have previously reported that immunization with complementary peptide (denoted RhCA 67-16) for Torpedo α-acetylcholine receptor (AChR), amino acid residues 61-76 (denoted AChR 61-76) induces the formation of anti-idiotype antibodies (anti-Id abs) and protects against the development of experimental autoimmune myasthenia gravis (EAMG). A mAb to RhCA67-16 (denoted TCM240, IgG1, kappa) also recognize the combining sites of abs against the main immunogenic region of the AChR. Recombinant protein of heavy chain of TCM240 showed higher affinity against RhCA67-16 peptide than that of recombinant protein of light chain of TCM240. Amino acid residues 100-116 of the AChR represent the dominant T cell epitope, which is important in helping Ab response to this autoantigen. Thus, selective inactivation of CD4+ AChR-specific T helper cells should lower AChR Ab levels and ameliorate disease. Immunization with complementary peptide against AChR 100-116 induced polyclinic and monoclonal Ab (CTCR8, IgG2b, kappa), which inhibited the AChR 100-116 stimulation of AChR-sensitized lymphocytes and recognized Vb 15 containing T cell receptors on AChR 100-116-specific T cell lines and clones ; lowered AChR Ab levels ; reduced the loss of muscle AChR ; and lessened the incidence and severity of EAMG. Inhibition of T cell proliferation by CTCR8 mAb was due to T cell anergy induction. These findings suggest a new strategy for treatment of MG.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Shigeru Araga et al.: "A completementary peptide vaccine that induces T cell anergy and prevents experimental allergic neuritis in Lewis rats"163. 476-482 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shigeru Araga et al.: "A peptide vaccine that prevents experimental autuimmune myasthenia gravis by specifically blocking T cell help"FASEB Journal. 14. 185-196 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 荒賀 茂 他: "Complementary T-cell epitope peptideに対するmonoclonal抗体が認識するEAMGのTCR"Neuroimmunology. 5. 82-83 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 荒賀 茂 他: "重症筋無力症でのidiotype抗体を認識するモノクローナル抗体のDNA解析"Neuroimmunology. 6. 148-149 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 荒賀 茂 他: "重症筋無力症患者のbinding抗体を認識するTCM240抗体のrecombinant蛋白の作成"Neuroimmunology. 7. 162-163 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 荒賀 茂 他: "重症筋無力症患者での結合抗体を認識するコンプリメンタリーペプチド抗体"Neuroimmunology. 7. 233-238 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada,H., S.Araga, T.Takeshima, K.Nakashima.: "Plasam lactic acid and pyruvic acid levels in patients with chronic primary headaches during the headache free period"Yonago Acta Medica. 40. 13-19 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada,H., S.Araga, , T.Takeshima, K.Nakashima: "Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache"Headache. 38. 39-42 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Araga,S., M,Kishimoto, S.Doi and K,Nakashima: "A complementary peptide vaccine that induces T cell anergy and prevents experimental allergic neuritis in Lewis rats"J. Immunol.. 163. 476-482 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Araga,S., L.Xu, K, Nakashima, M.Villain and J.E.Blalock: "A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help"FASEB J.. 14. 185-196 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 荒賀茂也: "A complementary peptide vacine that induces Tcellaneray and prevents EAN in Leurs rats"J.Jmmunology. 163. 476-482 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒賀茂也: "重症筋無力症疾患者のbinding抗体を認識するTCM240抗体のrecombinant蛋白の作製"Neuroimmunology. 7. 162-163 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒賀茂也: "重症筋無力症疾患者のblocking抗体を認識するコンプリメンタリーペプチド抗体"Neuroimmunology. 7. 233-238 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒賀茂也: "EANを抑制するコンプリメンタリーペプチド抗体によるT細胞anergyの導入"Neuroimmunology. 8. 94-95 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒賀茂也: "Apeptide uaccine that prevents EAMlr by specifically blocking Tcell help"FASEB Journal. 14. 185-196 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 荒賀 茂ほか: "重症筋無力症患者のbinding抗体を認識するTCM240抗体のrecombinant蛋白の作成" 神経免疫学. 7. 162-163 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 荒賀 茂: "コンプリメンタリーペプチドによる抗原特異免疫抑制療法" 医学のあゆみ. 185. 951-954 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Okada, S.Araga et al.: "Plasma Lactic acid Pyruvic acid levels in migracne and tension type hendache" Heagache. 38. 39-42 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] ARAGA,S: "Tcell receptor Vβ8.3 dominates the P2 protein response in Lewis rat experimental alleigic reuritin" J.Allergy Clinical Immnology. 99. S282- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 荒賀,茂ほか: "重症筋無力症でのidiotype抗体を認識するモノクロナール抗体のDNA解析" 神経免疫学. 6. 148-149 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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