1Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
Sci Signal. 2011 Jul 19;4(182):ra47. doi: 10.1126/scisignal.2001765.
Whether thymocytes adopt an αβ or a γδ T cell fate in the thymus is determined at the β selection checkpoint by the relatively weak or strong signals that are delivered by either the pre-T cell receptor (preTCR) or the γδ TCR, respectively. Signal initiation at the β selection checkpoint is thought to be independent of ligand engagement of these receptors. Some reports have suggested that receptor oligomerization, which is thought to be mediated by either the immunoglobulin (Ig)-like domain of the preTCRα (pTα) chain or the variable domain of TCRδ, is a unifying mechanism that initiates signaling in early CD4(-)CD8(-) double-negative (DN) thymocyte progenitors. Here, we demonstrate that the extracellular regions of pTα and TCRδ that are implicated in mediating receptor oligomerization were not required for signal initiation from the preTCR or TCRγδ. Indeed, a truncated TCRγδ that lacked all of its extracellular Ig-like domains still formed a signaling-competent TCR that drove cells through the β selection checkpoint. These observations suggest that signal initiation in DN thymocytes is simply a consequence of the surface-pairing of TCR chains, with signal strength being a function of the abundances of surface TCRs. Thus, processes that regulate the surface abundances of TCR complexes in DN cells, such as oligomerization-induced endocytosis, would be predicted to have a major influence in determining whether cells adopt an αβ versus γδ T cell fate.
胸腺细胞在胸腺中是选择成为αβ T 细胞还是γδ T 细胞，这取决于其前 T 细胞受体（preTCR）或γδ TCR 分别传递的相对较弱或较强的信号。在β选择检查点，信号的起始被认为独立于这些受体的配体结合。一些报告表明，受体寡聚化可能是由 preTCRα（pTα）链的免疫球蛋白（Ig）样结构域或 TCRδ 的可变结构域介导的，这是一种启动早期 CD4(-)CD8(-)双阴性（DN）胸腺细胞祖细胞信号转导的统一机制。在这里，我们证明了 pTα 和 TCRδ 的细胞外区域介导受体寡聚化，但对于 preTCR 或 TCRγδ 的信号起始并不是必需的。事实上，一种缺乏所有细胞外 Ig 样结构域的截断 TCRγδ仍然形成了一种有信号能力的 TCR，可驱动细胞通过β选择检查点。这些观察结果表明，DN 胸腺细胞中的信号起始仅仅是 TCR 链的表面配对的结果，而信号强度是表面 TCR 丰度的函数。因此，调节 DN 细胞中 TCR 复合物表面丰度的过程，如寡聚化诱导的内吞作用，预计会对决定细胞选择成为αβ T 细胞还是γδ T 细胞命运产生重大影响。
