The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 19 March 2001.
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© The Rockefeller University Press, 0022-1007/2001/3/769/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 6, March 19, 2001 769-776

Brief Definitive Report

Induction of a Diverse T Cell Receptor {gamma}/{delta} Repertoire by the Helix-Loop-Helix Proteins E2a and Heb in Nonlymphoid Cells

Jimut Kanti Ghosha, William J. Romanowa, and Cornelis Murrea

a Division of Biology, University of California San Diego, La Jolla, California 92093

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 {gamma} and {delta} 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 {gamma} and {delta} 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 {gamma} and {delta} 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.

Key Words: E2A • HEB • recombination activating gene • T cell receptor {gamma} and {delta} rearrangements • chromatin accessibility

© 2001 The Rockefeller University Press


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