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Timing of somatic recombination in T-cell development Thymocytes rearrange their T-cell receptor loci and test these rearrangements at defined checkpoints before continuing their developmental process. Developing thymocytes can commit to the γδ T-cell lineage if they first productively rearrange their γ and δ T-cell receptor loci, or they can commit to the αβ T-cell lineage if they first productively rearrange their α and β T-cell receptor loci. There are three key checkpoints that a thymocyte must pass to continue development and become a functional naÏve T cell.
Timing of somatic recombination in T-cell development Checkpoint of the γδ subunits of the T-cell receptor-A thymocyte that has properly gone through development can only express either an α β T-cell receptor or a γ δ T-cell receptor. Rearrangement of the T-cell receptor loci begins at the β , γ, and δ genes, and a T cell that has properly recombined both the γ and δ chain loci is destined to become a γδ T cell.
Timing of somatic recombination in T-cell development Checkpoint of the β subunit of the T-cell receptor-This checkpoint occurs during the somatic recombination events to test the β chain of the T-cell receptor, which recombines at the same time as the γ and δ subunits. If the β subunit locus recombines properly, somatic recombination is inactivated to allow the thymocyte to ready itself for the next developmental stage.
Timing of somatic recombination in T-cell development Checkpoint of the gd subunits of the T-cell receptor-Once a thymocyte that has properly recombined a b chain locus and progressed to the next developmental stage, recombination events continue at the a, g, and d T-cell receptor genes. If the g and d genes recombine properly, the thymocyte will be committed to becoming a gd T cell.
Timing of somatic recombination in T-cell development Checkpoint of the a subunit of the T-cell receptor-The purpose of this checkpoint is to test the a subunit of the T-cell receptor, which recombines at the same time as the g and d subunits. Proper recombination of the a chain locus allows the thymocyte to continue development toward becoming an ab T cell.