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阿尔法贝塔T细胞受体中的一个基因通过调节ERK活动来控制积极选择
G Werlen1, B Hausmann, E Palmer
1Basel Institute for Immunology, Switzerland. werlen@bii.ch
Nature
|August 10, 2000
概括
胸腺中的积极选择需要特定的T细胞受体 (TCR) 信号. 一个突变的TCRα链动机损害了细胞外信号调节激酶 (ERK) 激活,这对积极选择至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 胸膜选择,包括正负选择,对于T细胞发育至关重要.
- 这两种过程都涉及到字母T细胞受体 (TCR) 和自我主要基因相容性复合体 (自我MHC) 的识别.
- 不同的信号通路可以控制正与负选择.
研究的目的:
- 为了调查不同的信号级联是否调节正和负的胸膜选择.
- 为了确定基因激活蛋白激酶 (MAPK) 级联在胸膜选择中的作用.
- 阐明通过TCR调解的积极选择的信号要求.
主要方法:
- 使用了表达突变TCRα链连接域 (α-CPM) 受体的转基因小鼠.
- 研究了各种MAPK级联的激活,包括细胞外信号调节激酶 (ERK).
- 评估了像Lck,ZAP-70,CD3zeta和LAT这样的信号分子对洗剂不溶性甘油脂丰富微域 (DIG) 的招募.
主要成果:
- 在TCR的α-CPM基因的突变选择性损害了积极选择.
- 积极选择的不能激活具有突变TCR的胸细胞中的ERK.
- 这种缺陷与Lck,ZAP-70,CD3zeta和LAT对DIG的招募减少相关.
结论:
- 持续的ERK激活,依赖于一个完好无损的DIG关联信号体,对于积极的胸膜选择至关重要.
- 这些发现表明,ERK信号在积极选择中起着特定的作用,与负面选择途径不同.
- 这凸显了DIG中信号分子对TCR介导的胸膜教育的细分的重要性.
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