THEMIS, a recently identified T-lineage-restricted protein, is the founding member of a large metazoan protein family. Gene inactivation studies have revealed a critical requirement for THEMIS during thymocyte positive selection, implicating THEMIS in signaling downstream of the T cell antigen receptor (TCR), but the mechanistic underpinnings of THEMIS function have remained elusive. A previous model posited that THEMIS prevents thymocytes from inappropriately crossing the positive/negative selection threshold by dampening TCR signaling. However, new data suggest an alternative model where THEMIS enhances TCR signaling enabling thymocytes to reach the threshold for positive selection, avoiding death by neglect. We review the data supporting each model and conclude that the preponderance of evidence favors an enhancing function for THEMIS in TCR signaling.

中文翻译：

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THEMIS：两种模型，不同的阈值

THEMIS是最近发现的T谱系限制蛋白，是大型后生蛋白家族的创始成员。基因失活研究揭示了在胸腺细胞阳性选择过程中对THEMIS的关键要求，这暗示THEMIS参与T细胞抗原受体（TCR）下游的信号传导，但是THEMIS功能的机制基础仍然难以捉摸。先前的模型提出，THEMIS通过抑制TCR信号传导来防止胸腺细胞不适当地越过阳性/阴性选择阈值。但是，新数据提示了THEMIS增强TCR信号传导能力，使胸腺细胞达到阳性选择阈值，避免因疏忽而死亡的替代模型。