| Project/Area Number |
09670657
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tottori University |
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Principal Investigator |
ARAGA Shigeru Faculty of Medicine, TOTTORI UNIVERSITY, Associate Professor., 医学部, 助教授 (40193065)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| 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)
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| Keywords | ANTI-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 |
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| 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.
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