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

CD62L + central memory CD8 + T (T CM ) 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 T CM cells harboring specific interaction hubs compared with naive CD8 + T cells, as observed at cytotoxic effector genes such as Ifng and Tbx21 . T CM cells also acquire de novo CTCF (CCCTC-binding factor) binding sites, which are not only strongly associated with T CM -specific hubs but also linked to increased activities of local gene promoters and enhancers. Specific ablation of CTCF in T CM cells 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 T CM cells serves as a chromatin architectural basis for their transcriptomic dynamics in primary response and for imprinting the code of "recall readiness" against secondary challenge.