Programming a Killer (CTL)

Microscopic image

CTL are killer lymphocytes that hold outstanding promise for controlling viral infections and cancer therapeutically, as they can be employed in adoptive immunotherapy and are the target of successful vaccination. The Pipkin lab has developed novel approaches to map the fundamental repeating structures of chromatin (nucleosomes) at unprecedented resolution, novel reporter genes to track cells in vivo that induce expression of Prf1, an essential gene that is required for the anti-tumor killing activity of CTL, and the only systems to conduct genome-scale pooled RNAi screens in T cells, in vivo, during the course of actual viral infections. Using these tools and approaches, the Pipkin lab is clarifying how transcription factors govern the specific organization of nucleosomes that enforces CTL differentiation, identifying the chromatin regulatory factors that maintain the differentiated state epigenetically, and demonstrating how these processes mediate durable immunity.