GADS REGULATES THE SIGNALING THRESHOLD THROUGH THE T CELL RECEPTOR

GADS 调节 T 细胞受体的信号阈值

基本信息

  • 批准号:
    7959692
  • 负责人:
  • 金额:
    $ 10.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-07-01 至 2010-06-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The T cell repertoire must be sufficiently diverse so that every pathogen we might encounter can be recognized and targeted for destruction. This great diversity must be regulated so that T cells do not recognize and destroy our own tissues and cause autoimmune diseases. The balance between broad immunologic diversity and restriction of the T cell repertoire to avoid autoimmunity is struck during the processes of positive and negative selection. When developing T cells first express a mature T cell receptor (TCR) complex, the cells are tested for their ability to recognize self-MHC complexes. Thymocytes expressing a TCR that binds MHC with high affinity undergo apoptosis via negative selection. Conversely, T cells that are unable to bind MHC undergo apoptosis via "death-by-neglect". Only T cells expressing a TCR that can bind MHC with moderate affinity are positively selected and continue to mature. The goal of this research project is to understand how TCR-proximal signaling events regulate downstream signaling pathways. We hypothesize that the Gads adaptor protein regulates the signaling threshold through the TCR. This hypothesis is based on previous observations showing that Gads-deficient mice have defects in positive and negative selection. Despite these defects, Gads-/- mice can generate mature T cells, indicating that Gads is not required for TCR-mediated signaling. To test our hypothesis, we will identify the Gads-dependent signaling pathways that are required for positive and negative selection. Then, we will determine how Gads regulates the signaling threshold through the TCR and, in turn, regulates the downstream signaling pathways.
这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金, 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 T细胞库必须足够多样化,以便我们可能遇到的每一种病原体都能被识别并被摧毁。这种巨大的多样性必须受到控制,这样T细胞才不会识别和破坏我们自己的组织,从而导致自身免疫性疾病。广泛的免疫多样性和限制T细胞库以避免自身免疫之间的平衡是在积极和消极选择的过程中取得的。当发育中的T细胞首先表达成熟的T细胞受体(TCR)复合体时,这些细胞被测试其识别自身MHC复合体的能力。表达与MHC高亲和力结合的TCR的胸腺细胞通过负选择发生凋亡。相反,不能与MHC结合的T细胞通过“疏忽而死”来进行细胞凋亡。只有表达TCR的T细胞才能以中等亲和力结合MHC,并继续成熟。本研究项目的目的是了解TCR-近端信号事件如何调节下游信号通路。我们假设GADS接头蛋白通过TCR调节信号阈值。这一假设是基于之前的观察结果,即GADS缺陷小鼠在正向选择和负向选择方面存在缺陷。尽管有这些缺陷,Gads-/-小鼠仍能产生成熟的T细胞,这表明TCR介导的信号转导不需要Gads。为了验证我们的假设,我们将确定正选择和负选择所需的依赖Gads的信号通路。然后,我们将确定Gads如何通过TCR调节信号阈值,进而调节下游信号通路。

项目成果

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THOMAS M. YANKEE其他文献

THOMAS M. YANKEE的其他文献

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{{ truncateString('THOMAS M. YANKEE', 18)}}的其他基金

The effects of morphine on the immune responses against HIV in vivo
吗啡对体内HIV免疫反应的影响
  • 批准号:
    7687913
  • 财政年份:
    2008
  • 资助金额:
    $ 10.13万
  • 项目类别:
The effects of morphine on the immune responses against HIV in vivo
吗啡对体内HIV免疫反应的影响
  • 批准号:
    7622446
  • 财政年份:
    2008
  • 资助金额:
    $ 10.13万
  • 项目类别:
THE ROLE OF THE GADS ADAPTOR PROTEIN IN CD28-MEDIATED IMMUNITY
GADS 适配器蛋白在 CD28 介导的免疫中的作用
  • 批准号:
    7720545
  • 财政年份:
    2008
  • 资助金额:
    $ 10.13万
  • 项目类别:
THE ROLE OF THE GADS ADAPTOR PROTEIN IN CD28-MEDIATED IMMUNITY
GADS 适配器蛋白在 CD28 介导的免疫中的作用
  • 批准号:
    7609895
  • 财政年份:
    2007
  • 资助金额:
    $ 10.13万
  • 项目类别:
THE GADS ADAPTOR PROTEIN IN T CELL-MEDIATED PREVENTION OF VIRAL PATHOGENESIS
T 细胞介导的病毒发病机制预防中的 GADS 接头蛋白
  • 批准号:
    7381288
  • 财政年份:
    2006
  • 资助金额:
    $ 10.13万
  • 项目类别:
THE ADAPTOR PROTEIN GADS IN CD28-MEDIATED IMMUNITY
CD28 介导的免疫中的衔接蛋白 GADS
  • 批准号:
    7170531
  • 财政年份:
    2005
  • 资助金额:
    $ 10.13万
  • 项目类别:
Flow Cytometry Core: Core 2
流式细胞术核心:核心 2
  • 批准号:
    8708132
  • 财政年份:
  • 资助金额:
    $ 10.13万
  • 项目类别:
Flow Cytometry Core: Core 2
流式细胞术核心:核心 2
  • 批准号:
    8461882
  • 财政年份:
  • 资助金额:
    $ 10.13万
  • 项目类别:
Flow Cytometry Core: Core 2
流式细胞术核心:核心 2
  • 批准号:
    9095397
  • 财政年份:
  • 资助金额:
    $ 10.13万
  • 项目类别:
Flow Cytometry Core: Core 2
流式细胞术核心:核心 2
  • 批准号:
    8539057
  • 财政年份:
  • 资助金额:
    $ 10.13万
  • 项目类别:

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