| Project/Area Number |
63870013
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
INOUE Keizo Univ. of Tokyo Fac. of Pharm. Professor, 薬学部, 教授 (30072937)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Kouji Toso Corp. Res. Center Researcher, 研究員
KANAI Noburo Toso Corp. Res. Center Head of Res. Inst., 所長
UMEDA Masato Univ. of Tokyo Fac. of Pharm. Assis. Prof., 薬学部, 助手 (10185069)
KUDO Ichiro Univ. of Tokyo Fac. of Pharm. Asso. Prof., 薬学部, 助教授 (30134612)
佐藤 和己 東ソー, 生物工学研究所, 研究員
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1989: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1988: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | monoclonal antibody / phospholipids / phospholipases / allergy / soy bean lipids / autoimmunity / auto antibody / thrombosis / リポプロテイン / ホスファチジルセリン / ホスファチジルコリン / 動脈硬化 / 脾内免疫法 / モノクローナル抗体 / ホスホリパーゼA_2 / ホスファチジルイノシトール4、5二燐酸 |
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| Research Abstract |
It is generally accepted that naturally abundant antigens such as membrane lipids and carbohydrates, or low molecular weight peptides with conserved amino acid sequences among species, are less immunogenic and it has been difficult to obtain monoclonal antibodies against these substances. In this study, we have established the methods for the effective production of monoclonal antibodies against these low immunogenic materials.
1) Phospholipid antigens :
We employed a system based on the direct immunization of phospholipid antigens into spleen to induce anti-phospholipid antibodies in normal subjects, and found that anti-phospholipid antibodies of IgG isotypes were effectively induced by the method. A series of monoclonal antibodies against phosphatidylserine and phosphatidylcholine were established. Analyses of reactivities and structures of anti-phospholipid monoclonal antibodies have provided a new insight into the etiology of anti-phospholipid antibodies in the so called "anti-phospholipid antibody syndromes".
2) Immune response against soy bean lipids :
Recent analyses have suggested that soy bean lipid is one of the strongest inducer of food allergies. In the course of studying the immune response to soy bean lipids, we found that auto antibodies against a particular serum component were frequently induced by the oral or intrasplenic administration of the lipids. Mechanism of the induction and etiology of this unique autoantibody is now under investigation.
3) Protein antigens :
Combination of intrasplenic immunization and 8-mercaptogua-nosine as an adjuvant have provided a useful method to produce monoclonal antibodies against low immunogenic protein antigens. By this method, we for the first time succeeded in producing monoclonal antibodies against phospholipases.
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