Ghosh J K, Romanow W J, Murre C
Division of Biology, University of California San Diego, La Jolla, CA 92093, USA.
J Exp Med. 2001 Mar 19;193(6):769-76. doi: 10.1084/jem.193.6.769.
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.
在胸腺细胞发育的特定阶段，T细胞受体（TCR）基因座由可变（V）、多样（D）和连接（J）基因片段组装而成。胸腺细胞发育过程中TCRγ和δ V（D）J的正确重排需要E2A蛋白的存在。我们在此表明，在重组激活基因（RAG）1和RAG2存在的情况下，E2A和一种密切相关的蛋白HEB各自都有能力在人肾细胞中激活TCRγ和δ重排。编码连接多样化，包含核苷酸缺失，且偶尔会出现P核苷酸。有趣的是，E2A和HEB蛋白仅靶向V、D和J片段的一个子集。因此，E2A和HEB使TCRγ和δ基因座对重组机制具有局部可及性。这些数据表明，仅通过V（D）J重组酶以及转录调节因子E2A和HEB的存在，就可以在非淋巴细胞中诱导出独特但多样的TCR库。
