REGULATION OF T-CELL RECEPTOR (TCR)-BETA LOCUS ALLELIC EXCLUSION AND INITIATION OF TCR-ALPHA LOCUS REARRANGEMENT IN IMMATURE THYMOCYTES BY SIGNALING THROUGH THE CD3 COMPLEX

During thymocyte differentiation, the T cell receptor (TCR)-beta genes are rearranged before the TCR-alpha genes. Immature CD4(-)8(-) double -negative thymocytes with a productive rearrangement of the TCR-beta l ocus are selected to continue maturation to the CD4(+)8(+) double-posi tive stage, driven by signals through the pre-TCR. The signals through the pre-TCR can be synchronized by injection of mice with anti-CD3 ep silon monoclonal antibody. Using this approach, we demonstrated coordi nated induction of a triad of responses in immature thymocytes: arrest . of V to DJ rearrangement in the TCR-beta locus, transient down-regul ation of rearrangement-activating gene (RAG)-1 and RAG-2 transcripts, and initiation of germ-line transcription of the TCR-alpha locus. Thes e results suggest that the transition from TCR-beta to TCR-alpha locus rearrangement is controlled by signal transduction through the pre-TC R.