Molecular Immunology and Signaltransduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
PLoS Biol. 2013;11(6):e1001589. doi: 10.1371/journal.pbio.1001589. Epub 2013 Jun 18.
Natural killer T (NKT) cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR.
自然杀伤 T（NKT）细胞的发育依赖于其半不变的 Vα14i-TCR 对自身糖脂的识别。然而，TCR 介导的信号在多大程度上决定成熟 NKT 细胞的身份和功能仍不完全清楚。为了解决这个问题，我们开发了一种小鼠品系，允许在 Tcrα 基因座内的内源性 Tcrα 基因座上条件性表达 Vα14i-TCR。我们证明，当用 Vα14i 限制性 TCR 替换其内源性 TCR 库时，幼稚 T 细胞被激活，但它们不会分化为 NKT 细胞。另一方面，在成熟的 NKT 细胞上诱导的 TCR 缺失不会影响它们的谱系身份、内稳态或先天快速细胞因子分泌能力。因此，我们提出外周 NKT 细胞对自身反应性 TCR 不敏感，因此是独立的。
