The biological activity of natural and mutant pTα alleles
The biological activity of natural and mutant pTα alleles
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DOI：
10.1084/jem.194.5.695
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发表时间：
2001-09-03
影响因子：
15.3
通讯作者：
Hayday, AC
中科院分区：
文献类型：
--
作者：
Gibbons, D;Douglas, NC;Hayday, AC
β选择是早期胸腺细胞分化的主要检查点，由前T细胞受体（TCR）的成功表达介导，前T细胞受体（TCR）包括TCR β链、CD 3蛋白和替代TCR α链pT α。前TCR的作用机制尚未解决。在人类和小鼠中，pT α基因编码两种RNA，pT α（a）和基本截短的形式pT α（B）。这项研究表明，这两种药物在拯救pT α（-/-）小鼠的多种胸腺细胞缺陷方面具有生物活性。pT α的其他活性等位基因包括缺乏主要胞外域和大部分长胞质尾（其在抗原受体链中是独特的）的等位基因，以及胞质尾被TCR C α的短尾取代的另一个等位基因。因此，pT α链的功能需要很少。这些数据支持一种假设，即pT α的主要作用是稳定前TCR，并且pT α的大部分保守结构可能起着关键的调节作用。
beta selection is a major checkpoint in early thymocyte differentiation, mediated by successful expression of the pre-T cell receptor (TCR) comprising the TCR beta chain, CD3 proteins, and a surrogate TCR alpha chain, pT alpha. The mechanism of action of the pre-TCR is unresolved. In humans and mice, the pT alpha gene encodes two RNAs, pT alpha (a), and a substantially truncated form, pT alpha (b). This study shows that both are biologically active in their capacity to rescue multiple thymocyte defects in pT alpha (-/-) mice. Further active alleles of pT alpha include one that lacks both the major ectodomain and much of the long cytoplasmic tail (which is unique among antigen receptor chains), and another in which the cytoplasmic tail is substituted with the short tail of TCR C alpha. Thus, very little of the pT alpha chain is required for function. These data support a hypothesis that the primary role of pT alpha is to stabilize the pre-TCR, and that much of the conserved structure of pT alpha probably plays a critical regulatory role.