Studies of cell-mediated immunity and autoantigen of paraneoplastic neuronal degeneration
| Project/Area Number |
11670648
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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 | Kanazawa Medical University |
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Principal Investigator |
SAKAI Koichiro Kanazawa Medical University, Department of Neurology, Assistant Professor, 医学部, 助教授 (70225754)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | paraneoplastic syndromes / ceretellaf degeneration / autoimmunity / DNA immunization / cytotoxic T iymphocytes / Two-hybrid system / NF-kappaB / cell cycle / 傍腫瘍性神経症候群 / MRG X / 自己抗原 / 組織適合抗原 / 小脳プルキンエ細胞 / ロイシンジッパー |
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| Research Abstract |
Paraneoplastic cerebellar degeneration (PCD) associated with gyncological and breast malignancies is a disorder in which an autoimmune mechanism has been suggested, and both antibody- and cell-mediated immune responses exist against pcd17/cdr2, a neural protein expressed cytotoxic T lymphocytes (CTLs) specific for PCD17/cdr2 are demonstrated in the blood of patients with PCD. (1) The functional roles of anti-neuronal CTLs in the pathogenesis of PCD are unknown. DNA immunization of mice with naked pcd17/cdr2 cDNA could induce anti-Purkinje cell cytoplasmic antibodies and CTLs that could lysis syngenic myeloma cells pulsed with PCD17 peptide. In spite of the generation of anti-Purkinje cell antibodies and PCD17-specific CTLs in vivo, neither clinical nor pathologic changes consistent with significant cerebellar degeneration have been detected. (2) The biological activities of PCD17/cdr2 are not knbwn. Co-transfection study demonstrated that PCD17/cdr2 can suppress the basal or activated NF-_-dependent transcriptional activity without binding to the consensus seuquence for NFkB, suggesting that pcd17 is a potential depressor for Nf-kB-dependent gene transcription in neurons. (3) The presence of a leucine zipper motif in the amino acid sequence of PCD17/cdr2 suggests that this protein might interact with other proteins harboring a leucine zipper motift. The present study showed that PCD17/cdr2 interacts with a nuclear helix-loop-helix leucine zipper protein, MRG X. Transfection studies with T98G glioblastoma cells suggested that MRG X which is thought to be functionally related with cell cycle and cell growth, may be regulated by PCD17/cdr2 in Purkinje cells.
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Report
(4 results)
Research Products
(19 results)
