Both TCRα and TCRδ Chain Diversity Are Regulated During Thymic Ontogeny

Abstract

TCRα and TCRδ chains are coded by a common genetic locus using a single set of V gene segments (ADV segments). This article addresses the question of regulation of the use of the ADV segments by the TCRα and TCRδ chains. Using both qualitative and quantitative analyses we have studied the use of 23 ADV gene families as part of TCRα and TCRδ transcripts. A number of previously undetected rearrangement and transcription events are described, indicating that the intrathymic TCRδ repertoire is much more diverse than previously supposed. Repertoire analysis at several developmental time points allowed the description of regulated waves of ADV gene use, not only for TCRδ chains, but also for TCRα chains, during thymic ontogeny. Control of these waves appears to be linked directly to the ADV segments and their local chromatin environment, which may change over the course of T cell differentiation.