Work

H2A.Z primes an epigenetic landscape for memory CD8+ T cell recall response

Year: 2025

Type: article

Abstract: The rapid recall ability is a hallmark of memory CD8+ T cells, but the underlying mechanisms remain incompletely understood. Here we find that histone variant H2A.Z is expressed at higher levels in memory CD8+ T cells than in naïve cells. Furthermore, in memory CD8+ T cells H2A.Z is deposited at the promoters and enhancers, particularly super enhancers, of those genes involved in recall responses, while H2A.Z deficiency in memory CD8+ T cells inhibits recall responses in vitro and in vivo. Mechanistically, multi-omics analyses show that H2A.Z maintains a poised epigenetic landscape on those recall response genes to potentiate a rapid transcription activation. Accordingly, H2A.Z deposition on these genes is induced by TCR/CD28 signals, and is cooperated by IL-7/IL-15 signals. Together, our data suggest that H2A.Z may orchestrate a specific epigenetic landscape during memory T cell differentiation to facilitate a rapid recall response. The ability to pursue a stronger recall response on secondary antigen encounter is a hallmark for T cell immunity. Here the authors show that the histone component, H2A.Z, may contribute to CD8 T cell recall readiness by depositing to specific locations and introducing a specific epigenetic landscape in CD8 memory T cells to facilitate more prompted activation of related genes.

Source: Nature Communications

DOI: 10.1038/s41467-025-62976-4