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

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Abstract

During specific stages of thymocyte development, the T cell receptor (TCR) locus is assembled from variable (V), diversity (D), and joining (J) gene segments. Proper TCR γ and δ V(D)J rearrangement during thymocyte development requires the presence of the E2A proteins. Here we show that E2A and a closely related protein, HEB, in the presence of recombination activating gene (RAG)1 and RAG2, each have the ability to activate TCR γ and δ rearrangement in human kidney cells. The coding joints are diverse, contain nucleotide deletions, and occasionally show the presence of P nucleotides. 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 γ and δ loci to the recombination machinery. These data indicate that a distinct but diverse TCR repertoire can be induced in nonlymphoid cells by the mere presence of the V(D)J recombinase and the transcriptional regulators, E2A and HEB.

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Ghosh, J. K., Romanow, W. J., & Murre, C. (2001). Induction of a diverse T cell receptor γ/δ repertoire by the helix-loop-helix proteins E2A and HEB in nonlymphoid cells. Journal of Experimental Medicine, 193(6), 769–775. https://doi.org/10.1084/jem.193.6.769

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