New insights into TCR β-selection

T cell receptor (TCR) beta-selection (herein referred to as beta-selection) is a pivotal checkpoint in mammalian T cell development when immature CD4-CD8- T-cells (thymocytes) express pre-TCR following successful Tcrb gene rearrangement. At this stage, alpha beta T cell lineage commitment and allelic exclusion to restrict one beta-chain per cell take place and thymocytes undergo a proliferative burst. beta-selection is known to be crucially dependent upon synchronized Notch and pre-TCR signaling; however, other necessary inputs have been identified over the past decade, expanding our knowledge and understanding of the beta-selection process. In this review, we discuss recent mechanistic findings that have enabled a more detailed decoding of the molecular dynamics of the beta-selection checkpoint and have helped to elucidate its role in early T cell development.