Sleckman B P, Bassing C H, Bardon C G, Okada A, Khor B, Bories J C, Monroe R, Alt F W
Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115, USA.
Immunol Rev. 1998 Oct;165:121-30. doi: 10.1111/j.1600-065x.1998.tb01235.x.
T-cell development is a complex and ordered process that is regulated in part by the progressive assembly and expression of antigen receptor genes. T cells can be divided into two lineages based on expression of either an alpha beta or gamma delta T-cell antigen receptor (TCR). The genes that encode the TCR beta and gamma chains lie in distinct loci, whereas the genes that encode the TCR alpha and delta chains lie in a single locus (TCR alpha/delta locus). Assembly of TCR variable region genes is mediated by a site-specific recombination process that is common among all lymphocytes. Despite the common nature of this process, recombination of TCR genes is tightly regulated within the context of the developing T cell. TCR beta, gamma and delta variable region genes are assembled prior to TCR alpha variable region genes. Furthermore, assembly of TCR beta variable region genes is regulated within the context of allelic exclusion. The regulation of rearrangement and expression of genes within the TCR alpha/delta locus presents a complicated problem. TCR alpha and delta variable region genes are assembled at different stages of T-cell development, and fully assembled TCR alpha and delta variable region genes must be expressed in distinct lineages of T cells, alpha beta and gamma delta, respectively. We have developed several experimental approaches to assess the role of cis-acting elements in regulating recombination and expression of TCR genes. Here we describe these approaches and discuss our analyses of the regulation of accessibility of the TCR beta and TCR alpha/delta loci during T-cell development.
T细胞发育是一个复杂且有序的过程，部分受抗原受体基因的逐步组装和表达调控。根据αβ或γδ T细胞抗原受体（TCR）的表达情况，T细胞可分为两个谱系。编码TCR β链和γ链的基因位于不同的基因座，而编码TCR α链和δ链的基因位于单个基因座（TCR α/δ基因座）。TCR可变区基因的组装由一种位点特异性重组过程介导，这在所有淋巴细胞中都很常见。尽管该过程具有共性，但TCR基因的重组在发育中的T细胞背景下受到严格调控。TCR β、γ和δ可变区基因在TCR α可变区基因之前组装。此外，TCR β可变区基因的组装在等位基因排斥的背景下受到调控。TCR α/δ基因座内基因的重排和表达调控是一个复杂的问题。TCR α和δ可变区基因在T细胞发育的不同阶段组装，并且完全组装的TCR α和δ可变区基因必须分别在αβ和γδ这两种不同的T细胞谱系中表达。我们已经开发了几种实验方法来评估顺式作用元件在调控TCR基因重组和表达中的作用。在此，我们描述这些方法，并讨论我们对T细胞发育过程中TCR β和TCR α/δ基因座可及性调控的分析。
