Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity

作者：Newman Dane M; Sakaguchi Shinya; Lun Aaron; Preston Simon; Pellegrini Marc; Khamina Kseniya; Bergthaler Andreas; Nutt Stephen L; Smyth Gordon K; Voss Anne K; Thomas Tim; Ellmeier Wilfried; Belz Gabrielle T^*; Allan Rhys S^*

来源：Cell Reports, 2016, 16(12): 3311-3321.

DOI：10.1016/j.celrep.2016.08.056

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 CD8 alpha beta 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 Cd8 alpha 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 E8(I) enhancer element. These findings suggest a direct role of CD8 alpha beta co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool.

• 出版日期2016-9-20
• 单位河北医科大学