Role of the pre-T cell receptor in lineage commitment

T细胞抗原受体（TCR）依赖性谱系定型是免疫球蛋白T细胞臂的关键特征。 免疫系统需要TCR特异性和T淋巴细胞的功能潜力。 CD4辅助细胞和CDSkiller细胞与II类和I类MHC的T细胞系定型机制 特异性受体已被广泛研究，最近的研究被压倒性地解释为 表明由不同TCR配体引发的不同TCR信号传导指示发育中的T细胞 发展成不同的血统。TCR γ S和TCR前体在γ 5与α P的发展中的作用 谱系细胞在T细胞发育的早期检查点目前尚不清楚。虽然很明显 TCR γ S和前TCR的特异性信号传导不同，并有助于谱系定型， 实验已经被解释为指示TCR的指导作用，而其他实验表明， 谱系定型是预先确定的，并且仅通过特定TCR的表达来确认。额外 在一些报道的实验中的复杂性是这样的事实，即特定TCR对 当实验不是在竞争条件下进行时，谱系承诺可能会被误判 即其中具有不同TCR的前体竞争小生境（空间）和资源（受体的配体 除了TCR）。在这里，我们建议区分指导性和验证性 TCR γ S、TCR α 0和前TCR在谱系定型中的作用，通过1.）T细胞发育分析 in.vivo和在体外在竞争性和非竞争性条件下用表达TCR γ S的前体， TCR α或TCR β转基因。将特别强调Notch信号在这一过程中的作用，2。 在诱导型γ和前TCR表达后作为时间函数的基因表达分析和3.）分析 通过RNAi敲低谱系特异性基因表达后的发育。

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.