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Acetylation of the Cd8 locus by KAT6A determines memory T cell diversity


Newman, DM; Sakaguchi, S; Lun, A; Preston, S; Pellegrini, M; Khamina, K; Bergthaler, A; Nutt, SL; Smyth, GK; Voss, AK; Thomas, T; Ellmeier, W; Belz, GT; Allan, RS
2016-09-20
Cell Rep
Journal Article
16
12
3311-21
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.
Cell Press
Molecular Immunology; Bioinformatics; Infection and Immunity; Development and Cancer
10.1016/j.celrep.2016.08.056
Refer to copyright notice on published article.

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Creation Date 2016-10-04 09:29:40 Last Modified 2016-10-04 11:50:21