Samelson L E, Lindsten T, Fowlkes B J, van den Elsen P, Terhorst C, Davis M M, Germain R N, Schwartz R H
Nature. 1985;315(6022):765-8. doi: 10.1038/315765a0.
The antigen receptor on T lymphocytes has recently been characterized as a heterodimeric, transmembrane glycoprotein consisting of disulphide-linked alpha (acidic) and beta (basic) subunits of relative molecular mass (Mr) 40,000-45,000 each. The genes encoding these proteins have been cloned and shown to resemble immunoglobulin genes in both overall structure and the requirement for DNA rearrangement before expression. In humans, three additional proteins, termed the T3 complex, are found associated with the clonotypic receptor, and a role for T3 in receptor expression has been proposed. Despite these recent advances in characterizing the antigen receptor complex, there is as yet little understanding of T-cell maturation, particularly the stage of T-cell ontogeny at which the genes encoding the antigen receptor and its associated structures are expressed and assembled. In the adult, stem cells destined to differentiate into T cells arise in the bone marrow and migrate to the thymus, where T-cell precursors proliferate, develop a preference for recognizing antigens in the context of self MHC molecules and are released to the periphery. Recently, cells that have the properties of immature murine thymocytes have been isolated and described. We have now analysed these cells with a series of molecular probes and we describe three distinct patterns of T-cell antigen receptor gene rearrangements in developing thymocytes.
T淋巴细胞上的抗原受体最近被鉴定为一种异二聚体跨膜糖蛋白,由相对分子质量(Mr)各为40,000 - 45,000的二硫键连接的α(酸性)和β(碱性)亚基组成。编码这些蛋白质的基因已被克隆,并且在总体结构以及表达前DNA重排的需求方面都显示出与免疫球蛋白基因相似。在人类中,发现另外三种被称为T3复合物的蛋白质与克隆型受体相关联,并且有人提出T3在受体表达中起作用。尽管在表征抗原受体复合物方面最近取得了这些进展,但对T细胞成熟,特别是对抗原受体及其相关结构进行编码的基因在T细胞个体发育的哪个阶段表达和组装,目前仍知之甚少。在成年人中,注定要分化为T细胞的干细胞在骨髓中产生并迁移到胸腺,在那里T细胞前体增殖,形成在自身MHC分子背景下识别抗原的偏好,然后释放到外周。最近,已分离并描述了具有未成熟小鼠胸腺细胞特性的细胞。我们现在用一系列分子探针分析了这些细胞,并描述了发育中的胸腺细胞中T细胞抗原受体基因重排的三种不同模式。