Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Phys Biol. 2012 Aug;9(4):045005. doi: 10.1088/1478-3975/9/4/045005. Epub 2012 Aug 7.
Interaction of the T cell receptor (TCR) with pathogen-derived peptide presented by the major histocompatibility complex (pMHC) molecule is central to adaptive immunity as it initiates intracellular signaling to trigger T cell response to infection. Kinetic parameters of this interaction have been under intensive investigation for more than two decades using soluble pMHCs and/or TCRs with at least one of them in the solution (three-dimensional (3D) methods). Recently, several techniques have been developed to enable kinetic analysis on live T cells with pMHCs presented by surrogate antigen presenting cells (APCs) or supported planar lipid bilayers (two-dimensional (2D) methods). Comparison of 2D versus 3D parameters reveals drastic differences with broader ranges of 2D affinities and on-rates and orders of magnitude faster 2D off-rates for functionally distinct pMHCs. Here we review new 2D data and discuss how it may impact previously developed models of T cell discrimination between pMHCs of different potencies.
T 细胞受体(TCR)与主要组织相容性复合体(MHC)分子呈递的病原体衍生肽的相互作用是适应性免疫的核心,因为它启动细胞内信号转导,触发 T 细胞对感染的反应。使用可溶性 pMHC 和/或 TCR(其中至少有一种在溶液中),对这种相互作用的动力学参数进行了二十多年的密集研究(三维(3D)方法)。最近,已经开发了几种技术,能够在具有替代抗原呈递细胞(APC)呈递的 pMHC 的活 T 细胞上进行动力学分析,或在支持的平面脂质双层(二维(2D)方法)上进行动力学分析。二维与三维参数的比较显示出明显的差异,二维亲和力和结合速率的范围更宽,功能不同的 pMHC 的二维离解速率快几个数量级。在这里,我们回顾新的 2D 数据,并讨论它如何影响之前开发的 T 细胞区分不同效力的 pMHC 的模型。