Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Immunology. 2010 Mar;129(3):322-8. doi: 10.1111/j.1365-2567.2009.03241.x.
The interaction of T cells with antigen-presenting cells is the hallmark of adaptive immunity. In vitro studies have described the formation of an immunological synapse between these cells, and intra-vital imaging has described in great detail the dynamics of these interactions. The immunological synapse has become a paradigm to study signals exchanged between the two cells. A wealth of information has been amassed regarding the localization of signalling molecules, their kinetics and the transcription factors they activate. We continue to discover mechanisms that cause receptors and signalling molecules to compartmentalize in the cell; however, the emerging challenge lies in understanding how the immunological synapse contributes to differentiation. Here, we review some of the transcription factors activated downstream of T-cell receptor signalling and discuss mechanisms by which antigen dose and affinity may influence differentiation. Antigen affinity might change the kind of transcription factors that are activated whereas antigen dose is likely to influence the temporal dynamics of the transcription factors. The immunological synapse is therefore likely to influence differentiation by modulating the trafficking of transcription factors and by promoting asymmetric cell division, an emerging concept.
T 细胞与抗原呈递细胞的相互作用是适应性免疫的标志。体外研究已经描述了这些细胞之间形成免疫突触,而活体成像则详细描述了这些相互作用的动态。免疫突触已成为研究两个细胞之间信号交换的范例。关于信号分子的定位、动力学及其激活的转录因子,已经积累了大量信息。我们不断发现导致受体和信号分子在细胞内区室化的机制;然而,新出现的挑战在于理解免疫突触如何有助于分化。在这里,我们回顾了 T 细胞受体信号转导下游激活的一些转录因子,并讨论了抗原剂量和亲和力如何影响分化的机制。抗原亲和力可能改变被激活的转录因子的类型,而抗原剂量可能影响转录因子的时间动态。因此,免疫突触可能通过调节转录因子的运输和促进不对称细胞分裂来影响分化,这是一个新兴概念。