The signals that dictate whether a thymocyte will express the αß or γδ T-cell receptors are unknown. Although it is also not known if these two different cell types use identical recombinational machinery during rearrangement, the same variable (V) region genes can be used by both α and δ chains. By examining the products of rearrangements in αß or γδ thymocytes that express identical V genes, we hoped to determine whether these cell types might differ in particular aspects of their recombinational activity. The polymerase chain reaction was used to show that the Tcrd-V2, Tcrd-V3, and Tcra-V3 genes are expressed as both Tcra and Tcrd transcripts in fetal and adult BALB/c mice. Sequencing of Vδ3 isolates was performed in order to compare the contribution of various mechanisms to the generation of junctional diversity. Extensive junctional diversity was present at all stages of development examined (fetal, newborn, and adult). During early development both α and δ chain junctional diversity is generated primarily by variability in the position of joining two gene segments (i.e., Tcrd-V3 to Tcra-J in α chains; Tcrd-V3 to Tcrd-D2 and Tcrd-D2 to Tcrd-J1 in δ chains). The pattern of base pair deletion from the end of the Tcrd-V3 gene was identical in α and δ chains and deletions occurred in fetal as well as adult T cells. In later development T cells use not only this mechanism for α and δ chains but also the addition of bases at gene segment junctions, presumably through the action of terminal deoxynucleotidyl transferase (TdT). Finally, a comparison of the variable domains of these α and δ chains shows that a notable difference is the variability in length of the CDR 3 region which can be significantly longer in δ-chains than in α-chains.
ASJC Scopus subject areas