Würch A, Biro J, Potocnik A J, Falk I, Mossmann H, Eichmann K
Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany.
J Exp Med. 1998 Nov 2;188(9):1669-78. doi: 10.1084/jem.188.9.1669.
During alpha beta thymocyte development, the clonotypic alpha beta-T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR-CD3 complex: the pre-TCR, containing a clonotypic TCR-beta chain and invariant pre-Talpha, is expressed on pre-T cells before rearrangement of the TCR-alpha locus. Moreover, clonotype-independent CD3 complexes (CIC) appear on pro-T cells before VDJ rearrangements of TCR-beta genes. The pre-TCR is known to mediate TCR-beta selection, the prerequisite for maturation of CD4(-)8(-) double negative (DN) thymocytes to the CD4(+)8(+) double positive stage. A developmental function of CIC has so far not been delineated. In mice single deficient and double deficient for CD3zeta/eta and/or p56(lck), we observe a pronounced reduction in the proportions of CD25(+) DN thymocytes that express intracellular TCR-beta chains. TCR-beta transcripts are reduced in parallel with TCR-beta polypeptide chains whereas no reduction in TCR-beta locus rearrangements could be detected. Wild-type levels of TCR-beta transcripts and of cells expressing TCR-beta polypeptide chains are induced by treatment with anti-CD3epsilon mAb. The data suggest that the initial expression of rearranged TCR-beta VDJ genes in pro-T cell to pre-T cell progression is dependent on CD3 complex signaling, and thus define a putative developmental function for CIC.
在αβ型胸腺细胞发育过程中，克隆型αβ-T细胞受体（TCR）之前会依次表达TCR-CD3复合物的未成熟版本：前TCR，包含克隆型TCR-β链和不变的前Tα，在TCR-α基因座重排之前在前T细胞上表达。此外，在TCR-β基因的VDJ重排之前，克隆型非依赖性CD3复合物（CIC）出现在前T细胞上。已知前TCR介导TCR-β选择，这是CD4(-)8(-)双阴性（DN）胸腺细胞成熟到CD4(+)8(+)双阳性阶段的先决条件。迄今为止，CIC的发育功能尚未明确。在CD3ζ/η和/或p56(lck)单缺陷和双缺陷的小鼠中，我们观察到表达细胞内TCR-β链的CD25(+)DN胸腺细胞比例明显降低。TCR-β转录本与TCR-β多肽链平行减少，而未检测到TCR-β基因座重排减少。用抗CD3ε单克隆抗体处理可诱导野生型水平的TCR-β转录本和表达TCR-β多肽链的细胞。数据表明，在前T细胞向T细胞发育过程中，重排的TCR-β VDJ基因的初始表达依赖于CD3复合物信号传导，从而确定了CIC的一种假定发育功能。
