Dissecting the Transcriptional Control of Human MAIT Cell Identity and Function by PLZF and Helios

About This Grant

Project Summary This project aims to uncover the transcriptional and metabolic mechanisms that govern the identity, function, and therapeutic potential of mucosal-associated invariant T (MAIT) cells, a non-MHC-restricted, innate-like T cell subset with growing relevance in cancer and infectious disease immunotherapy. By leveraging two clinically relevant molecular glues—CC-647 and DKY-709—that selectively degrade the transcription factors PLZF and Helios, we will precisely manipulate the transcriptional programs of MAIT cells and related innate-like lymphocytes ( T and NK cells) in primary human samples. Using integrated transcriptomic, epigenomic, metabolic, and functional profiling, this study will define how PLZF and Helios sustain MAIT cell effector poise, tissue-homing capacity, and metabolic restraint. The outcomes will enable the rational design of engineered MAIT cells with optimized persistence and functionality for off-the-shelf immunotherapies.