| Project/Area Number |
14370159
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Tohoku University |
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Principal Investigator |
HATTORI Toshio Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30172935)
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| Co-Investigator(Kenkyū-buntansha) |
ASHINO Yugo Tohoku University, Hospital, Research Associate, 病院・助手 (20361082)
SANO Kunio Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20192601)
岡田 信司 東北大学, 医学部附属病院, 講師 (50312575)
大野 勲 東北大学, 大学院・医学系研究科, 助教授 (00250762)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | gp41 / HIV / antibody / AIDS / vaccine / gp120 / ペプチド / モノクロナル抗体 / 立体構造 / R5 / X4 / V3グループ / fusogenic form / raft / エピトープ |
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| Research Abstract |
To understand the mechanisms of HIV infection, we clarified that N terminus of V3 loop of BH-10 clone is responsible for its binding to the cells. We also treated the surface of H9/IIIB cells by several proteases including thrombin and analyzed the expression of functional epitomes by FACS. Thrombin treatment decreased the binding of anti-V3 mAb while enhanced the bindings of mAbs against Co-receptor binding site, a CD4 binding site and neutralizing epitope of gp41. Thrombin also enhanced fusion between H9/IIIB and MAGI cells. These findings support that blood borne inflammatory molecule thrombin activate gp 120 and enhanced the fusion.
We also evaluated monoclonal antibodies (mAbs) against the gp41 core structure such as mAbs 50.69, 98.6 and T26, by western blotting and flow cytometry. Western blotting showed mAbs 50.69 and 98.6 bound to both monomeric and oligomeric gp41 and mAb T26 exclusively bound to oligomeric gp41. We evaluated the sera from pneumocystis pneumonia patients (PCP) and long term survivors (LTS). The results revealed that PCP sera as well as LTS sera inhibited the binding of all the three mAbs, and the PCP sera inhibited mAb T26 binding efficiently than LTS. Therefore PCP patients retain competing immunity to antibodies against not only the shared epitopes of the core structure (binding sites of mAbs 50.69 and 98.6) but also against oligomeric gp41 specific epitope (binding site of mAb T26).
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