| Project/Area Number |
18K19507
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 52:General internal medicine and related fields
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Morio Tomohiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30239628)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | エピトープマッピング / HLA / 分子模倣 / 感染症 / 自己免疫疾患 |
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| Outline of Final Research Achievements |
This study is based on a completely novel hypothesis. We tried to prove >30 mer peptides could bind to multiple class I MHC molecules as well as both class I and class II molecules, could serve as mini-super antigen. We call the peptide as shared broad-reactive antigen (SRBA). We extracted candidate SBRA regions by using a computational tool for prediction of HLA binding site such as NetMHC4.0 server, and also examined the binding experiment using several long peptides to multiple MHC molecules. To that end, we prepared several K562 model cells that express single HLA molecule that is common in Japanese population. Using the cells, we showed evidence that single peptide can bind to different HLA and that single long peptide binds to both class I and class II molecules. We established more than 10 multiple-virus specific T cells. By using them, we established a method to detect intracellular IFNg, IL4, IL10, IL2, TNFa, and MIP1b, and expression of CD107a (indicator of degranulation).
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により私たちが提唱したSRBAが実際に存在しうることが明らかになった。詳細には明らかに出来なかったが、この長鎖ペプチドは免疫刺激にも抑制にも働くことが明らかになった。これは全く新しい概念である。これを展開することで、長鎖ペプチドによるリンパ球の活性化や比較的安定な免疫作動薬の開発など、新しい技術や治療法の開発に繋がる可能性がある。現在様々な新型ウイルス感染症が問題になっている。この際にも様々なペプチドなどを用いて、ウイルス抗原がどのような免疫系を駆動するかを明らかにし、病態を明らかにし、また疾患の重篤度や合併症に関わる重要な知見を与えるものことに寄与することが期待される。
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