| Project/Area Number |
24590591
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | The Institute of Physical and Chemical Research |
|---|
Principal Investigator |
HASHIMOTO-TANE Akiko 独立行政法人理化学研究所, 統合生命医科学研究センター, 研究員 (10415226)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | T細胞 / 免疫シナプス / T細胞受容体 / 受容体クラスター / インテグリン / ミオシン / 蛍光イメージング / 全反射顕微鏡 / 免疫シグナル / ミオシンII / 免疫 / シグナル伝達 / アクチン / 受容体シグナル / モーター分子 |
|---|
| Outline of Final Research Achievements |
In this study, we tried to reveal the mechanism for translation of TCR stimulation strength through quantitative imaging analysis of TCR microcluster (TCR-MC), which is a minimum assemble to start T cell activation. We performed proteome analysis and fluorescent imaging, and found that each TCR-MC was transiently bordered by a ring of focal adhesion molecules during the initial stage of T cell activation. The ring structure, which we named the microsynapse, is composed of LFA-1 and focal adhesion molecules such as paxillin, Pyk2 and the core structure of the TCR-MC. The microsynapse is supported by integrin outside-in signals, F-actin and myosin II activity. Perturbation of the microsynapse induced impairment of TCR-MC formation, reduced SLP76 recruitment, and resulted in impaired cellular signaling and function in vitro and in vivo. Thus, the microsynapse supports weak TCR response through integrin outside-in signals and is a critical structure for T cell activation.
|
