ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8 T Cell Effector and Memory Responses.

CD8 T cells are critical for the immune response to pathogens and tumors, and CD8 T cell memory protects against repeat infections. In this study, we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of CD8 T cell immune responses. Mice with a T cell-specific deletion of ATF7ip have a CD8 T cell-intrinsic enhancement of expression and expression leading to enhanced effector and memory responses. Chromatin immunoprecipitation sequencing studies identified ATF7ip as a repressor of and gene expression through the deposition of the repressive histone mark H3K9me3 at the gene and intergenic region. Interestingly, ATF7ip targeted transposable elements for H3K9me3 deposition at both the locus and the intergenic region, indicating that ATF7ip silencing of transposable elements is important for regulating CD8 T cell function. These results demonstrate a new epigenetic pathway by which IL-7R and IL-2 production are constrained in CD8 T cells, and this may open up new avenues for modulating their production.