Shutter J, Cain J A, Ledbetter S, Rogers M D, Hockett R D
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mol Cell Biol. 1995 Dec;15(12):7022-31. doi: 10.1128/MCB.15.12.7022.
T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell.
根据αβ或γδ T细胞受体(TCR)的表达情况,T细胞可分为两组。由于TCR δ链基因座位于较大的TCR α链基因座内,因此在T细胞发育过程中,控制这两种受体的利用对于确定T细胞类型很重要:α基因座的重排导致δ编码片段的缺失,并决定向αβ谱系分化。在发育中的胸腺中,会发生相对位点特异性重组,通过这种重组,TCR δ链基因片段被删除。这种删除会去除所有的Dδ、Jδ和Cδ基因,并且在两个等位基因上都会发生。这种δ删除机制在小鼠和人类之间是进化保守的。构建了转基因小鼠,其包含人类δ删除元件以及尽可能多的内部TCR δ链编码序列,但不允许形成完整的δ链基因。培育出了几个转基因品系,这些品系显示转基因内的删除元件之间发生了重组。这些品系表明,δ删除元件在脾脏和胸腺的αβ T细胞中发挥作用。这些重组在γδ群体中很少见,这表明δ删除元件的利用机制在αβ T细胞中起作用,而在γδ T细胞中不存在。此外,已经鉴定出了一个离散的早期胸腺细胞群体,这些细胞含有δ删除元件重组,但没有Vα到Jα重排。这些数据与一个模型一致,即δ删除有助于实现一种信号,通过该信号,TCR α链基因座进行重排和表达,从而成为αβ T细胞。