Sugahara S, Kuwano Y, Sato K, Hasegawa K, Yamagiwa S, Kawamura T, Yoshida Y, Asakura H, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
Scand J Immunol. 1998 Dec;48(6):592-604. doi: 10.1046/j.1365-3083.1998.00474.x.
Conventional T cells (i.e. TCRhigh) are generated by the main stream of T-cell differentiation in the thymus. However, primordial T cells (i.e. TCRint) are generated by extrathymic pathways and an alternative intrathymic pathway. Since TCRint cells contain self-reactive clones, the diversity of the T-cell antigen receptor (TCR) complementarity-determining region (CDR) 3 was examined. The predominant Vbeta8.2+ clones among TCRint cells were selected for DNA sequencing. Thymectomized, irradiated mice subjected to bone-marrow transplantation (BMT) were used; graft-versus-host disease (GVHD), B6-->(B6xC3H/He)F1 and syngeneic BMT, B6-->B6. In these combinations, only TCRint cells were generated. Vbeta8.2+ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vbeta8.2+ cells of TCRint and TCRhigh cells in normal mice were polyclonal, showing that the former has a lower diversity of CDR3 than the latter. The clonality of activated TCRhigh cells was examined, in which CD3high cells (bml2 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vbeta8.2+ clones among TCRhigh cells were expanding but the diversity of CDR3 was greater than that of CD3int cells, despite the fact that the recognition site of the H-2 difference was smaller. Taken together with invariant usage of V alpha14, these results suggest that TCRint cells have a low diversity of CDR3 of Vbeta genes.
传统T细胞（即TCR高表达细胞）由胸腺中T细胞分化的主流途径产生。然而，原始T细胞（即TCR中等表达细胞）由胸腺外途径和一条替代性胸腺内途径产生。由于TCR中等表达细胞包含自身反应性克隆，因此对T细胞抗原受体（TCR）互补决定区（CDR）3的多样性进行了检测。选择TCR中等表达细胞中占主导地位的Vbeta8.2 +克隆进行DNA测序。使用接受骨髓移植（BMT）的胸腺切除、经辐射的小鼠；移植物抗宿主病（GVHD），B6→（B6×C3H/He）F1和同基因BMT，B6→B6。在这些组合中，仅产生TCR中等表达细胞。在GVHD小鼠中，V基因CDR3多样性低的Vbeta8.2 +细胞得以扩增。正常小鼠中TCR中等表达细胞和TCR高表达细胞的Vbeta8.2 +细胞是多克隆的，这表明前者的CDR3多样性低于后者。检测了活化的TCR高表达细胞的克隆性，其中将CD3高表达细胞（bml2小鼠）注射到接受1 Gy辐射的B6裸鼠中。TCR高表达细胞中的一些Vbeta8.2 +克隆正在扩增，但尽管H-2差异的识别位点较小，其CDR3的多样性仍大于CD3中等表达细胞。结合V alpha14的不变使用情况，这些结果表明TCR中等表达细胞的Vbeta基因CDR3多样性较低。
