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通过TCR马三角转基因阻断αβT细胞发育

M Bonneville¹, I Ishida, P Mombaerts

¹Howard Hughes Medical Institute, Cambridge, Massachusetts 02139.

|December 21, 1989

概括

阿尔法贝塔T细胞的发展需要一个沉默元件来抑制马链基因表达. 如果没有这种沉声器,T细胞的发育就会被阻碍,从而支持一种新的T细胞分化模式.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
发展生物学发展生物学

背景情况:

T淋巴细胞对于适应性免疫至关重要,通过T细胞受体 (TCR) 识别抗原.
TCRs是异构体,可以是αβ或gamma delta,在不同的T细胞系表达.
从常见的T细胞前体到这些独特的血统的发育途径仍然不完全理解.

研究的目的:

调查控制T细胞的血统承诺的机制.
测试转录性沉声元件在αβT细胞发育中的作用.

主要方法:

产生和分析马三角形转基因小鼠.
研究与玛链基因相关的特定转录沉声元件和没有特有的转录沉声元件的小鼠T细胞发育.

主要成果:

缺乏静音元件的转基因小鼠显示严重阻断了αβT细胞生成.
这一发现与这样一个假设相矛盾,即马三角基因重排序在αβT细胞发育之前.
抑制马链基因表达对于αβT细胞发育至关重要.

结论:

一种转录性沉声元件在调节T细胞发育方面发挥着至关重要的作用.
沉声器模型,它假定抑制马链表达的αβT细胞的生成,得到了这些发现的强烈支持.

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