Induction of a diverse T cell receptor gamma/delta repertoire by the helix-loop-helix proteins E2A and HEB in nonlymphoid cells

During specific stages of thymocyte development, the T cell receptor (TCR) locus is assembled from variable (V), diversity (D), and joining (J) gene s egments. Proper TCR gamma and delta V(D)J rearrangement during thymocyte de velopment requires the presence of the E2A proteins. Here we show that E2A and a closely related protein, HEB, in the presence of recombination activa ting gene (RAG)1 and RAG2, each have the ability to activate TCR gamma and delta rearrangement in human kidney cells. The coding joints are diverse, c ontain nucleotide deletions, and occasionally show the presence of P nucleo tides. Interestingly, only a subset of V, D, and J segments are targeted by the E2A and HEB proteins. Thus, E2A and HEB permit localized accessibility of the TCR gamma and delta loci to the recombination machinery. These data indicate that a distinct but diverse TCR repertoire can be induced in nonl ymphoid cells by the mere presence of the V(D)J recombinase and the transcr iptional regulators, E2A and HEB.