Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK; Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Department of Biological Engineering, Columbia University, New York, NY 10027, USA.
Cell Rep. 2018 Jan 9;22(2):340-349. doi: 10.1016/j.celrep.2017.12.052.
T cells engage in two modes of interaction with antigen-presenting surfaces: stable synapses and motile kinapses. Although it is surmised that durable interactions of T cells with antigen-presenting cells involve synapses, in situ 3D imaging cannot resolve the mode of interaction. We have established in vitro 2D platforms and quantitative metrics to determine cell-intrinsic modes of interaction when T cells are faced with spatially continuous or restricted stimulation. All major resting human T cell subsets, except memory CD8 T cells, spend more time in the kinapse mode on continuous stimulatory surfaces. Surprisingly, we did not observe any concordant relationship between the mode and durability of interaction on cell-sized stimulatory spots. Naive CD8 T cells maintain kinapses for more than 3 hr before leaving stimulatory spots, whereas their memory counterparts maintain synapses for only an hour before leaving. Thus, durable interactions do not require stable synapses.
T 细胞与抗原呈递表面的相互作用有两种模式:稳定的突触和能动的结合突触。虽然推测 T 细胞与抗原呈递细胞的持久相互作用涉及突触,但原位 3D 成像无法解析相互作用的模式。我们已经建立了体外 2D 平台和定量指标,以确定 T 细胞在面临空间连续或受限刺激时的细胞内在相互作用模式。除了记忆 CD8 T 细胞之外,所有主要的静止人类 T 细胞亚群在连续刺激表面上更多时间处于结合突触模式。令人惊讶的是,我们在细胞大小的刺激点上没有观察到相互作用模式和耐久性之间的任何一致性关系。幼稚 CD8 T 细胞在离开刺激点之前保持结合突触超过 3 小时,而它们的记忆对应物在离开之前仅保持突触 1 小时。因此,持久的相互作用不需要稳定的突触。