Poster Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Fine-tuning of the CD8 co-receptor via a histone acetyltransferase determines memory T cell potential  (#344)

Dane M Newman 1 , Aaron Lun 1 , Simon Preston 1 , Marc Pellegrini 1 , Stephen L Nutt 1 , Anne K Voss 1 , Gordon K Smyth 1 , Tim Thomas 1 , Rhys S Allan 1 , Gabrielle T Belz 1
  1. WEHI, Parkville, VIC, Australia

During an immune response functionally diverse populations of pathogen-specific killer T cells are generated. Exactly how these populations arise is unclear. Here we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation is critical for guiding this lineage fate choice. We have identified a histone acetyltransferase (HAT) that is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. HAT-deficient CD8+ T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding correlated with reduced Cd8α mRNA transcripts and reduced histone H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in HAT-deficient T cells correlated with reduced TCR signalling intensity and accelerated contraction of the short-lived effector compartment, whereas the long-lived memory compartment appeared unaffected. This data suggests a direct role of CD8αβ co-receptor expression and histone acetylation in shaping functional diversity within the expanding cytotoxic T cell pool.