Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nat Immunol. 2011 May 22;12(7):647-54. doi: 10.1038/ni.2033.
Polarization of the T cell microtubule-organizing center (MTOC) toward the antigen-presenting cell (APC) is driven by the accumulation of diacylglycerol (DAG) at the immunological synapse (IS). The mechanisms that couple DAG to the MTOC are not known. By single-cell photoactivation of the T cell antigen receptor (TCR), we found that three distinct isoforms of protein kinase C (PKC) were recruited by DAG to the IS in two steps. PKC-ɛ and PKC-η accumulated first in a broad region of membrane, whereas PKC-θ arrived later in a smaller zone. Functional experiments indicated that PKC-θ was required for MTOC reorientation and that PKC-ɛ and PKC-η operated redundantly to promote the recruitment of PKC-θ and subsequent polarization responses. Our results establish a previously uncharacterized role for PKC proteins in T cell polarity.
T 细胞微管组织中心（MTOC）向抗原呈递细胞（APC）的极化是由免疫突触（IS）处二酰甘油（DAG）的积累驱动的。将 DAG 与 MTOC 偶联的机制尚不清楚。通过对 T 细胞抗原受体（TCR）的单细胞光激活，我们发现三种不同的蛋白激酶 C（PKC）同工型通过 DAG 分两步被募集到 IS。PKC-ɛ 和 PKC-η 首先在膜的一个宽区域内积累，而 PKC-θ 则较晚到达一个较小的区域。功能实验表明，PKC-θ 对于 MTOC 重新定向是必需的，并且 PKC-ɛ 和 PKC-η 冗余地起作用以促进 PKC-θ 的募集和随后的极化反应。我们的结果确立了 PKC 蛋白在 T 细胞极性中以前未被表征的作用。
