Antigen exposure reshapes chromatin architecture in central memory CD8+ T cells and imprints enhanced recall capacity [CUT&RUN]

Compared with naïve CD8+ T cells, antigen-experienced effector and central memory CD8 T cells show extensive CTCF redistribution and 3D genome reorgainzation, which underlie the transcriptomic diversification as well as recall capacity in response to secondary challenges. P14 CD8+ T cells were first transferred into B6.SJL mice followed by LCMV-Arm infection. On day 8 post-infection, KLRG1+IL-7Ra– P14 cells were sorted as effector CD8+ T (Teff) cells, and After ≥30 days, CD62L+ P14 cells were sorted as central memory (Tcm) cells were sorted. The sorted cells were subjected to CTCF CUT&RUN analysis.

与初始CD8+ T细胞相比，抗原暴露的效应性与中枢记忆性CD8 T细胞存在广泛的CCCTC结合因子（CTCF）重分布及三维基因组重塑，这一过程是其转录组多样性形成以及应对次级挑战时回忆应答能力的分子基础。研究人员首先将P14 CD8+ T细胞转输至B6.SJL小鼠体内，随后以淋巴细胞脉络丛脑膜炎病毒-Armstrong株（LCMV-Arm）感染小鼠。感染后第8天，分选KLRG1阳性、IL-7Ra阴性的P14细胞作为效应性CD8+ T（Teff）细胞；于感染后≥30天，分选CD62L阳性的P14细胞作为中枢记忆性（Tcm）细胞。对分选得到的细胞开展CTCF CUT&RUN分析。