GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306052/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306052GEOGSEfalseEpigenetic training licenses naïve CD8⁺ T cell metabolic fitness and functionNaïve T cells maintain quiescence yet must respond rapidly to antigens, but how they prime this capacity is unclear. We identify histone variant H2A.Z as a key regulator of an epigenetic training program that licenses quiescent naïve CD8+ T cells for future activation. H2A.Z deficiency disrupts naïve T cell homeostasis and effector responses. Multi-omics reveals that H2A.Z is selectively deposited at OXPHOS gene promoters in quiescent naïve CD8+ T cells, priming the chromatin for rapid transcriptional induction. This training is developmentally instructed by tonic IL-7 signaling and regulated by transcription factor GABPα. Age-related decline in IL-7 signaling reduces H2A.Z occupancy and impairs T cell activation, while IL-7 supplementation or enforced H2A.Z expression rescues this defect. H2A.Z overexpression also enhances CAR-T cell stemness and antitumor efficacy. Our work defines an IL-7R–GABPα–H2A.Z–OXPHOS axis that epigenetically establishes metabolic and functional fitness in quiescent T cells, offering insights for immunotherapy targeting ageing and tumors.2026/08/10GSE306052GSM9192149GSM9192167GSM9192145GSM9192146GSM9192168GSM9192169GSM9192147GSM9192148GSM9192152GSM9192130GSM9192174GSM9192175GSM9192153GSM9192131GSM9192132GSM9192154GSM9192155GSM9192133GSM9192170GSM9192171GSM9192172GSM9192150GSM9192173GSM9192151GSM9192138GSM9192139GSM9192156GSM9192134GSM9192135GSM9192157GSM9192158GSM9192136GSM9192159GSM9192137GSM9192141GSM9192163GSM9192164GSM9192142GSM9192165GSM9192143GSM9192166GSM9192144GSM9192160GSM9192161GSM9192162GSM919214034290306052Mus musculus