Regulation of T cell receptor (TCR)‐β locus allelic exclusion and initiation of TCR‐α locus rearrangement in immature thymocytes by signaling through the CD3 complex

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Abstract
During thymocyte differentiation, the T cell receptor (TCR)-β genes are rearranged before the TCR-α genes. Immature CD4−8− double-negative thymocytes with a productive rearrangement of the TCR-β locus are selected to continue maturation to the CD4+8+ double-positive stage, driven by signals through the pre-TCR. The signals through the pre-TCR can be synchronized by injection of mice with anti-CD3ϵ monoclonal antibody. Using this approach, we demonstrated coordinated induction of a triad of responses in immature thymocytes: arrest of V to DJ rearrangement in the TCR-β locus, transient down-regulation of rearrangement-activating gene (RAG)-1 and RAG-2 transcripts, and initiation of germ-line transcription of the TCR-α locus. These results suggest that the transition from TCR-β to TCR-α locus rearrangement is controlled by signal transduction through the pre-TCR.