Alternative splicing of rearranged T cell receptor δ sequences to the constant region of the α locus

The T cell receptor (TCR) α/δ locus is composed of a common, shared set of variable (V) and distinct diversity (D), joining (J), and constant (C) genes. It has been recognized for several years that transcripts of the rearranged VDJδ or VJα genes are spliced to the Cδ or Cα genes, respectively, encoding distinct TCR δ and α proteins. Herein, we describe the discovery of a splicing variation that allows the assembled VDJδ genes to be fused with the Cα gene. This variation is prominent in TCRδ gene-deficient mice but is also detectable in wild-type mice. Furthermore, we show that several in-frame VDJδ rearrangements in TCRδ gene-deficient mice are strikingly underrepresented, suggesting that the alternative transcripts, with protein coding capacity, influence the development of αβ thymocytes. In-frame TCRγ gene rearrangements do not appear underrepresented, indicating that the effect is not mediated by the γ chain. Instead, indirect evidence supports the hypothesis that the δ/α chimeric protein acts in conjunction with the TCRβ chain. These results have implications for the transcriptional control of the TCRα/δ locus and provide a novel insight into the distinct functional capacities of the TCR α and δ proteins during thymocyte development.