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1999 Fiscal Year Final Research Report Summary

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
KeywordsANTI-IDIOTYPE ANTIBODIES / IDIOTYPE ANTIBODIES / COMPLEMENTARY PEPTIDE / MYASTHENIA GRAVIS / pGEM VECTOR / PiPoin Xa-1 VECTOR
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.

  • Research Products

    (10 results)

All Other

All Publications (10 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2001-10-23  

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