A new transcript in the TCRB locus unveils the human ortholog of the mouse pre-Dβ1 promoter

Abstract

Introduction While most transcripts arising from the human T Cell Receptor locus reflect fully rearranged genes, several germline transcripts have been identified. We describe a new germline transcript arising from the human TCRB locus. Methods cDNA sequencing, promoter, and gene expression analyses were used to characterize the new transcript. Results The new germline transcript encoded by the human TCRB locus consists of a new exon of 103 bp, which we named TRBX1 (X1), spliced with the first exon of gene segments Cβ1 or Cβ2. X1 is located upstream of gene segment Dβ1 and is therefore deleted from a V‐DJ rearranged TCRB locus. The X1‐Cβ transcripts do not appear to code for a protein. We define their transcription start and minimal promoter. These transcripts are found in populations of mature T lymphocytes from blood or tissues and in T cell clones with a monoallelic TCRB rearrangement. In immature thymocytes, they are already detectable in CD1a−CD34+CD4−CD8− cells, therefore before completion of the TCRB rearrangements. Conclusions The X1 promoter appears to be the ortholog of the mouse pre‐Dβ1 promoter (PDβ1). Like PDβ1, its activation is regulated by Eβ in T cells and might facilitate the TCRB rearrangement process by contributing to the accessibility of the Dβ1 locus.