Lucien Turner, Tran Ngoc Van Le, Eric Cross, Clemence Queriault, Montana Knight, Krittin Trihemasava, James Davis, Patrick Schaefer, Janet Nguyen, Jimmy Xu, Brian Goldspiel, Elise Hall, Kelly Rome, Michael Scaglione, Joel Eggert, Byron Au-Yeung, Douglas C Wallace, Clementina Mesaros, Joseph A Baur, Will Bailis
Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, we identify nicotinamide adenine dinucleotide (NAD) biosynthesis as a biochemical hub for the T cell receptor affinity-dependent metabolome. Through this central anabolic role, we found that NAD biosynthesis governs a quiescence exit checkpoint, thereby pacing proliferation...
March 15, 2024: Science Immunology