可视化T细胞在配体检测过程中动态微绒毛的搜索与稳定过程。
Visualizing dynamic microvillar search and stabilization during ligand detection by T cells.
作者信息
Cai En, Marchuk Kyle, Beemiller Peter, Beppler Casey, Rubashkin Matthew G, Weaver Valerie M, Gérard Audrey, Liu Tsung-Li, Chen Bi-Chang, Betzig Eric, Bartumeus Frederic, Krummel Matthew F
机构信息
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Biological Imaging Development Center, University of California, San Francisco, CA 94143, USA.
出版信息
Science. 2017 May 12;356(6338). doi: 10.1126/science.aal3118.
During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet and quantum dot-enabled synaptic contact mapping microscopy to show that anomalous diffusion and fractal organization of microvilli survey the majority of opposing surfaces within 1 minute. Individual dwell times were long enough to discriminate pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized microvilli. Stabilization was independent of tyrosine kinase signaling and the actin cytoskeleton, suggesting selection for avid TCR microclusters. This work defines the efficient cellular search process against which ligand detection takes place.
在免疫监视过程中，T细胞会检查抗原呈递细胞的表面。在寻找负载肽的主要组织相容性复合体（pMHC）时，它们必须解决速度和灵敏度之间的经典权衡问题。长期以来，人们一直认为T细胞上的微绒毛充当感觉器官以实现搜索，但其策略尚不清楚。我们使用晶格光片和量子点介导的突触接触映射显微镜来表明，微绒毛的异常扩散和分形组织可在1分钟内检查大部分相对表面。单个驻留时间足够长，以区分pMHC半衰期，并且T细胞受体（TCR）积累选择性地稳定了微绒毛。稳定化独立于酪氨酸激酶信号传导和肌动蛋白细胞骨架，这表明对avid TCR微簇的选择。这项工作定义了进行配体检测的有效细胞搜索过程。
Zotero 插件