Instructional role of ligand in γδ T cell lineage commitment (153.42)

Abstract

Abstract The processes that influence alphabeta versus gammadelta T cell lineage commitment are not well defined. Evidence suggests that strength and duration of TCR signaling during T cell development can directly influence fate decisions, irrespective of the TCR isotype. Accordingly, T cell progenitors expressing a gammadelta TCR can be directed toward the alphabeta lineage when signaling through the TCR is attenuated. Previously, we showed that KN6 gammadelta TCR transgenic thymocytes can be directed to the alphabeta lineage when the KN6 TCR ligand, T-10/22, is eliminated. Here we investigate the impact of ligand affinity on cell fate as well as whether it regulates fate selection instructively or stochastically. These issues are addressed in vitro using the OP9 stromal cell model where ligand expression can be manipulated. Our data suggest that differences in ligand expression and affinity are important determinants in fate selection. Moreover, ligand appears to be influencing lineage-fate in an instructional manner and is associated with characteristic changes in gene expression. Understanding how modulating TCR signaling affects T cell lineage commitment will provide insight into pathways that control fate decisions of developing alphabeta or gammadelta T cells.