Journal article
Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity
DM Newman, S Sakaguchi, A Lun, S Preston, M Pellegrini, K Khamina, A Bergthaler, SL Nutt, GK Smyth, AK Voss, T Thomas, W Ellmeier, GT Belz, RS Allan
Cell Reports | CELL PRESS | Published : 2016
Open access
Abstract
How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A) is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. KAT6A-deficient CD8+ T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding linked to reduced Cd8α transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR sig..
View full abstractGrants
Awarded by Australian Research Council
Funding Acknowledgements
We thank Lucy Sullivan and Andrew Brooks for reagents. This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (to T.T., A.K.V., M.P., S.L.N., G.K.S., G.T.B., and R.S.A.), the Australian Research Council (to S.L.N., G.T.B., and R.S.A.). Work in the laboratory of W.E. was supported by the Austrian Science Fund (FWF): P23641, P26193, P23669, and P27747. Work in the laboratory of A.B. was supported by the Austrian Science Fund (FWF): P25360. This study was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme and by the Australian Cancer Research Fund.