Perica Karlo, Kosmides Alyssa K, Schneck Jonathan P
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Institute of Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Biochim Biophys Acta. 2015 Apr;1853(4):781-90. doi: 10.1016/j.bbamcr.2014.09.001. Epub 2014 Sep 6.
Artificial antigen presenting cells (aAPCs) are engineered platforms for T cell activation and expansion, synthesized by coupling T cell activating proteins to the surface of cell lines or biocompatible particles. They can serve both as model systems to study the basic aspects of T cell signaling and translationally as novel approaches for either active or adoptive immunotherapy. Historically, these reductionist systems have not been designed to mimic the temporally and spatially complex interactions observed during endogenous T cell-APC contact, which include receptor organization at both micro- and nanoscales and dynamic changes in cell and membrane morphologies. Here, we review how particle size and shape, as well as heterogenous distribution of T cell activating proteins on the particle surface, are critical aspects of aAPC design. In doing so, we demonstrate how insights derived from endogenous T cell activation can be applied to optimize aAPC, and in turn how aAPC platforms can be used to better understand endogenous T cell stimulation. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.
人工抗原呈递细胞(aAPC)是用于T细胞激活和扩增的工程平台,通过将T细胞激活蛋白偶联到细胞系表面或生物相容性颗粒上合成。它们既可以作为研究T细胞信号传导基本方面的模型系统,也可以作为主动或过继性免疫疗法的新方法用于转化研究。从历史上看,这些简化系统并非设计用于模拟内源性T细胞与抗原呈递细胞(APC)接触过程中观察到的时空复杂相互作用,这些相互作用包括微观和纳米尺度上的受体组织以及细胞和膜形态的动态变化。在此,我们综述了颗粒大小和形状,以及T细胞激活蛋白在颗粒表面的异质分布,是aAPC设计的关键方面。在此过程中,我们展示了如何将源自内源性T细胞激活的见解应用于优化aAPC,以及反过来aAPC平台如何用于更好地理解内源性T细胞刺激。本文是名为:纳米级膜组织与信号传导的特刊的一部分。