Activated CD8⁺ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 toward the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc-translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.

激活的 CD8 ⁺ T 淋巴细胞分化为异质亚群。使用超分辨率成像，我们发现在第一次分裂之前，动力蛋白依赖性囊泡运输将活性TORC1极化至近极的微管组织中心（MTOC）。这种活性 TORC1 与活性 eIF4F 物理相关，而 eIF4F 是 c -myc mRNA翻译所需的。结果，c -myc翻译多聚核糖体极化向靠近免疫突触的细胞极，导致局部 c -myc翻译。分裂时，TORC1-eIF4A 复合物优先分选到近端子细胞，促进不对称 c-Myc 合成。第一次分裂时 eIF4A 活性的短暂破坏使长期细胞命运轨迹偏向于类似记忆的功能。使用遗传条形码方法，我们发现第一次分裂姐妹细胞通常表现出转录谱差异，这些差异很大程度上与 c-Myc 和 TORC1 靶基因相关。我们的研究结果提供了关于如何在第一次分裂期间建立不同的 T 细胞命运轨迹的机制见解。