Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors.
Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors.
复制标题
DOI：
10.1038/ni.3560
复制
发表时间：
2016-12
影响因子：
30.5
通讯作者：
Singer A
中科院分区：
文献类型：
--
作者：
Kimura MY;Thomas J;Tai X;Guinter TI;Shinzawa M;Etzensperger R;Li Z;Love P;Nakayama T;Singer A
胸腺中 CD8+ T 细胞的主要组织相容性复合物 I 类 (MHC I) 阳性选择要求 T 细胞抗原受体 (TCR) 信号传导及时结束，以便细胞因子诱导 Runx3d（CD8 谱系转录因子）。我们检查了这些事件所需的时间，发现小鼠中所有 CD8+ 胸腺细胞的阳性选择的总体持续时间相似，尽管 TCR 信号传导时间明显不同。值得注意的是，延长的 TCR 信号时间通过细胞因子加速 Runx3d 诱导和加速分化为 CD8+ T 细胞来平衡。因此，除非 MHC I-TCR 信号传导时间过长以致 CD4 谱系特异性转录因子 ThPOK 表达，从而阻止 Runx3d 诱导，否则谱系错误不会发生。因此，我们的结果确定了一种补偿信号机制，通过在 MHC I 正选择过程中动态调节 Runx3d 诱导率来防止谱系命运错误。
Major histocompatibility complex class I (MHC I) positive selection of CD8+ T cells in the thymus requires that T cell antigen receptor (TCR) signaling end in time for cytokines to induce Runx3d, the CD8-lineage transcription factor. We examined the time required for these events and found that the overall duration of positive selection was similar for all CD8+ thymocytes in mice, despite markedly different TCR signaling times. Notably, prolonged TCR signaling times were counter-balanced by accelerated Runx3d induction by cytokines and accelerated differentiation into CD8+ T cells. Consequently, lineage errors did not occur except when MHC I–TCR signaling was so prolonged that the CD4-lineage-specifying transcription factor ThPOK was expressed, preventing Runx3d induction. Thus, our results identify a compensatory signaling mechanism that prevents lineage-fate errors by dynamically modulating Runx3d induction rates during MHC I positive selection.
登录
查看更多内容
DOI：
10.1038/nri2416
发表时间：
2008-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Taniuchi, I;Osato, M;Littman, DR
通讯作者：
Littman, DR
DOI：
10.1084/jem.20030170
发表时间：
2003-06-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bosselut R;Guinter TI;Sharrow SO;Singer A
通讯作者：
Singer A
影响因子：
32.4
作者：
Chong, MMW;Cornish, AL;Kay, TWH
通讯作者：
Kay, TWH
影响因子：
64.8
作者：
He, X;He, X;Kappes, DJ
通讯作者：
Kappes, DJ