Laboratoire Adhésion Cellulaire et Inflammation, Parc Scientifique de Luminy, Aix-Marseille Université, 13288 Marseille Cedex 09, France.
J Immunol. 2013 Sep 1;191(5):2064-71. doi: 10.4049/jimmunol.1300523. Epub 2013 Jul 29.
Adaptive immune responses are triggered by the rapid and sensitive detection of MHC-bound peptides by TCRs. The kinetics of early TCR/APC contacts are incompletely known. In this study, we used total internal reflection fluorescence microscopy to image human T cell membranes near model surfaces: contact was mediated by mobile protrusions of <0.4 μm diameter. The mean lifetime of contacts with a neutral surface was 8.6 s. Adhesive interactions increased mean contact time to 27.6 s. Additional presence of TCR ligands dramatically decreased contact to 13.7 s, thus evidencing TCR-mediated triggering of a pulling motion within seconds after ligand encounter. After an interaction typically involving 30-40 contacts formed during a 1-min observation period, TCR stimulation triggered a rapid and active cell spreading. Pulling events and cell spreading were mimicked by pharmacological phospholipase Cγ1 activation, and they were prevented by phospholipase Cγ1 inhibition. These results provide a quantitative basis for elucidating the earliest cell response to the detection of foreign Ags.
适应性免疫反应是由 TCR 对 MHC 结合肽的快速和敏感检测触发的。早期 TCR/APC 接触的动力学尚不完全清楚。在这项研究中，我们使用全内反射荧光显微镜来观察模型表面附近的人 T 细胞膜：接触是通过直径小于 0.4 μm 的可移动突起介导的。与中性表面的接触平均寿命为 8.6 秒。黏附相互作用将平均接触时间增加到 27.6 秒。TCR 配体的额外存在将接触时间显著缩短至 13.7 秒，从而证明 TCR 介导的在配体接触后几秒钟内引发牵拉运动。在 1 分钟观察期内通常涉及 30-40 个接触的相互作用后，TCR 刺激引发了快速而活跃的细胞扩展。牵拉事件和细胞扩展可被药理学磷脂酶 Cγ1 激活模拟，并且可被磷脂酶 Cγ1 抑制所阻止。这些结果为阐明对外来抗原检测的最早细胞反应提供了定量基础。
