Antigen exposure reshapes chromatin architecture in central memory CD8+T cells and imprints enhanced recall capacity

Abstract

CD62L+central memory CD8+T (TCM) cells provide enhanced protection than naive cells; however, the underlying mechanism, especially the contribution of higher-order genomic organization, remains unclear. Systematic Hi-C analyses reveal that antigen-experienced CD8+T cells undergo extensive rewiring of chromatin interactions (ChrInt), with TCMcells harboring specific interaction hubs compared with naive CD8+T cells, as observed at cytotoxic effector genes such asIfngandTbx21. TCMcells also acquire de novo CTCF (CCCTC-binding factor) binding sites, which are not only strongly associated with TCM-specific hubs but also linked to increased activities of local gene promoters and enhancers. Specific ablation of CTCF in TCMcells impairs rapid induction of genes in cytotoxic program, energy supplies, transcription, and translation by recall stimulation. Therefore, acquisition of CTCF binding and ChrInt hubs by TCMcells serves as a chromatin architectural basis for their transcriptomic dynamics in primary response and for imprinting the code of “recall readiness” against secondary challenge.