Regulation of the TCRα repertoire by the survival window of CD4+CD8+ thymocytes
- 22 April 2002
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 3 (5) , 469-476
- https://doi.org/10.1038/ni791
Abstract
T cell receptor (TCR) α alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRα rearrangement in orphan nuclear receptor RORγ-deficient mice, in which the DP lifespan is shorter, and in Bcl-xL–transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary Vα to Jα rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-xL induces a bias towards 3′ Jα usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the Jα locus and the opportunities for positive selection, thereby regulating the TCRα repertoire.Keywords
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