Preferential rearrangements of the T cell receptor-delta-deleting elements in human T cells.

Abstract

Abstract The major part of the TCR-delta locus is flanked by the so-called TCR-delta-deleting elements deltaRec and psi(J)alpha, which preferentially rearrange to each other in human thymocytes. On the basis of our combined Southern blot and PCR analyses, we also identified the prominent deltaRec-Jalpha58 rearrangement and three other preferential deltaRec rearrangements. The latter rearrangements concern deltaRec rearrangements to the Ddelta3, Jdelta1, and Jdelta3 gene segments. These deltaRec rearrangements do not delete the complete TCR-delta locus and are homologous to Vdelta-Jdelta rearrangements, because the majority of their junctional regions contain Ddelta gene segments. In contrast, the prominent deltaRec-psi(J)alpha and deltaRec-Jalpha58 rearrangements, representing approximately 68 and approximately 23% of all deltaRec rearrangements, respectively, are homologous to Valpha-Jalpha rearrangements, because Ddelta gene segments are absent in their junctional regions. Additional PCR analysis of Vdelta-psi(J)alpha and Vdelta-Jalpha58 coding and signal joints revealed also that these rearrangements resemble Valpha-Jalpha rearrangements, except for Vdelta2-psi(J)alpha and Vdelta2-Jalpha58 rearrangements, which resemble Vdelta-Jdelta rearrangements. Our data show that virtually all TCR-delta-deleting rearrangements are Valpha-like, and the high frequency of these rearrangements in the human thymus suggests that most thymocytes use these rearrangements to further differentiate into the TCR-alphabeta lineage. Based on the very low frequency of deltaRec and psi(J)alpha rearrangements in 4% of the T cell acute lymphoblastic leukemia patients (n = 151) and 6% of the T cell lines (n = 26), we hypothesize that rearranged TCR-delta-deleting elements exist for only an extremely short period during thymocyte differentiation, probably due to rapid subsequent Valpha-Jalpha rearrangements.