期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：31
页码：12729-12734
DOI：10.1073/pnas.0902621106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：During antigen recognition by T cells, signaling molecules on the T cell engage ligands on the antigen-presenting cell and organize into spatially distinctive patterns. These are collectively known as the immunological synapse (IS). Causal relationships between large-scale spatial organization and signal transduction have previously been established. Although it is known that receptor transport during IS formation is driven by actin polymerization, the mechanisms by which different proteins become spatially sorted remain unclear. These sorting processes contribute a facet of signal regulation; thus their elucidation is important for ultimately understanding signal transduction through the T cell receptor. Here we investigate protein cluster size as a sorting mechanism using the hybrid live T cell-supported membrane system. The clustering state of the co-stimulatory molecule lymphocyte function-associated antigen-1 (LFA-1) is modulated, either by direct antibody crosslinking or by crosslinking its intercellular adhesion molecule-1 ligand on the supported bilayer. In a mature IS, native LFA-1 generally localizes into a peripheral ring surrounding a central T cell receptor cluster. Higher degrees of LFA-1 clustering, induced by either method, result in progressively more central localization, with the most clustered species fully relocated to the central zone. These results demonstrate that cluster size directly influences protein spatial positioning in the T cell IS. We discuss a sorting mechanism, based on frictional coupling to the actin cytoskeleton, that is consistent with these observations and is, in principle, extendable to all cell surface proteins in the synapse.
关键词：actin ; mechanobiology ; membrane ; transport ; receptor
