Differential usage of δ recombining element and Vδ genes during T-cell ontogeny

Abstract

We analyzed the usage of the δ recombining element (δRec) and six Vδ genes in cell samples from 15 patients with CD3- and 10 patients with CD3+ T-cell acute lymphoblastic leukemia in an attempt to define the hierarchy of genetic events that is associated with the T-cell receptor (TCR) α/δ gene complex during T-cell ontogeny. Based on the deletion patterns of these genes, we surmised their relative order on chromosome 14 to be as follows: 5'-Vδ4, Vδ6, Vδ1, Vδ5, δRec, Vδ2, Dδ1-3, Jδ1-3, Cδ, Vδ3-3'. In agreement with previous reports, Vδ1 was found to be preferentially rearranged in CD3+ samples. In CD3- samples, Vδ2 and Vδ3 rearrangements were observed at a high frequency. Incomplete VδDδ rearrangements using Vδ2 or Vδ3, which are closest to Cδ, were observed in three patients with CD3- and one patient with CD3+. These results suggest that Vδ2- and Vδ3-(Dn)Dδ3 recombinations are among the earliest recombinational events. δRec was observed to be rearranged to φJα on one allele. In addition, δRec rearrangements to Jδ1 and Jα close to φJα were also demonstrated on three alleles and one allele, respectively. δRec rearrangements to Jδ and Jα other than φJα also inhibit expression of the TCR δ locus. Approximately half of the alleles with Jδ rearrangements showed no involvement of known Vδ or δRec, indicating the existence of other, yet-uncharacterized Vδ or δRec-like segments.