| First Author | Newman DM | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 12 | Pages | 3311-3321 |
| PubMed ID | 27653692 | Mgi Jnum | J:239117 |
| Mgi Id | MGI:5824961 | Doi | 10.1016/j.celrep.2016.08.056 |
| Citation | Newman DM, et al. (2016) Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity. Cell Rep 16(12):3311-21 |
| abstractText | 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 CD8alphabeta 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 Cd8alpha transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR signaling intensity and accelerated contraction of the effector-like memory compartment, whereas the long-lived memory compartment appeared unaffected, a result phenocopied by the removal of the Cd8 E8I enhancer element. These findings suggest a direct role of CD8alphabeta co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool. |
