Role of the pre-T cell receptor in lineage commitment

T细胞抗原受体(TCR)依赖的谱系承诺是T细胞臂的一个关键特征 协调T淋巴细胞TCR特异性和功能潜能所需的免疫系统。 CD4辅助细胞和CDS杀伤细胞与II类和I类MHC的T谱系承诺机制 已经对特定受体进行了广泛的研究，最近的研究被压倒性地解释为 表明由不同TCR配体启动的不同TCR信号指示发育中的T细胞 发展成不同的血统。TCRyS和前TCR在Y5-AP发病中的作用 T细胞发育的早期检查点的谱系细胞目前尚不清楚。虽然很明显， TCRyS和Pre-TCR的特定信号不同，并有助于血统承诺，一些 实验被解释为表明TCR的教育作用，而其他实验则表明 血统承诺是预先确定的，并且只有通过特定TCR的表达才能确认。一项额外的 在一些已报道的实验中，复杂的事实是特定TCR对 当实验不是在竞争条件下进行时，血统承诺可能会被误判 即，具有不同TCR的前体竞争利基(空间)和资源(受体的配体 而不是TCR)。在这里，我们建议区分指导性和确认性 TCRyS、TCRa0和前TCR在血统承诺中的作用T细胞发育分析 在体内和体外与表达TCRyS的前体竞争和非竞争条件下， TCRA或TCRp转基因。将特别强调Notch信号在这一过程中的作用，2.) 诱导后基因表达随时间变化的分析和前TCR的表达。分析 RNAi抑制谱系特异性基因表达后的发展。

T cell antigen receptor (TCR) dependent lineage commitment is a key feature of the T cell arm of the immune system that is required to align TCR specificity and functional potential of T lymphocytes. Mechanisms of T lineage commitment of CD4 helper and CDSkiller cells with class II and class I MHC- specific receptors have been studied extensively and recent studies were overwhelmingly interpreted to indicate that distinct TCR signaling that is initiated by different TCR ligands instructs developing T cells to develop into the different lineages. The role of TCRyS and the pre-TCR in development of y5 versus ap lineage cells at an earlier checkpoint in T cell development is at present not clear. While it is clear that specific signaling by the TCRyS and pre-TCR differs and contributes to lineage commitment, some experiments have been interpreted to be indicative of an instructive role of the TCR while others suggest that lineage commitment is predetermined and only confirmed by expression of a particular TCR. An additional complication in some of the reported experiments is the fact that the contribution of a particular TCR to lineage commitment can be misjudged when experiments are not conducted under competitive conditions i.e. where precursors with different TCRs compete for niches (space) and resources (ligands for receptors other than TCR) in the thymus. Here we propose to discriminate between an instructive and confirmatory role of the TCRyS, TCRa0 and the pre-TCR in lineage commitment by 1.) The analysis of T cell development in.vivo and in vitro under competitive and non-competitive conditions with precursors expressing TCRyS, TCRa or TCRp transgenes. Special emphasis will be given to the role of Notch-signaling in this process, 2.) Gene expression analysis as a function of time after inducible ySand pre-TCR expression and 3.) Analysis of development after knockdown of lineage-specific gene expression by RNAi.