Development of TCRB CDR3 length repertoire of human T lymphocytes
Development of TCRB CDR3 length repertoire of human T lymphocytes
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DOI：
10.1093/intimm/dxh046
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Kohsaka, H
中科院分区：
文献类型：
--
作者：
Nishio, J;Suzuki, M;Kohsaka, H
TCR的第三互补决定区（CDR 3）直接与结合到MHC分子凹槽的抗原肽相互作用。因此，它是启动获得性免疫和决定发育中胸腺细胞命运的最关键TCR结构。由于长度是定义CDR 3异质性的组分之一，因此已经在生理和病理条件下在来自人的各种T细胞亚群中研究了CDR 3长度库。然而，CDR 3长度库如何发展仅由少数报道解决，包括显示CD 4胸腺细胞的CDR 3在胸腺发育期间变得更短的报道。在这里，我们探索了胸腺和外周血中TCRB CDR 3长度库发育的多种调节。采用CDR 3长度谱分析来检查胸腺细胞和外周T细胞群体的CDR 3长度库。我们已经发现，库分布模式取决于BV基因的使用。BV依赖的模式在胸腺选择过程中形成，并在外周血中维持。在整个淋巴细胞发育过程中，观察到不同BV亚群之间平均CDR 3长度的差异。我们还观察到CD 4和CD 8胸腺细胞的CDR 3缩短。值得注意的是，缩短的程度取决于CD 4/CD 8谱系和BV基因的使用。当外周血T细胞克隆的扩增可以忽略不计时，成熟胸腺细胞与外周血淋巴细胞之间没有明显差异。因此，在淋巴细胞迁移到外周血中之前，TCRB CDR 3长度库在胸腺中被精细调节。
The third complementarity-determining region (CDR3) of TCR interacts directly with antigenic peptides bound to grooves of MHC molecules. Thus, it is the most critical TCR structure in launching acquired immunity and in determining fates of developing thymocytes. Since length is one of the components defining the CDR3 heterogeneity, the CDR3 length repertoires have been studied in various T cell subsets from humans in physiological and pathological conditions. However, how the CDR3 length repertoire develops has been addressed only by a few reports, including one showing that CDR3 of CD4 thymocytes becomes shorter during thymic development. Here, we explored multiple regulations on the development of the TCRB CDR3 length repertoires in the thymus and the peripheral blood. CDR3 length spectratyping was employed to examine thymocyte and peripheral T cell populations for their CDR3 length repertoires. We have found that repertoire distribution patterns depend on use of the BV gene. The BV-dependent patterns were shaped during thymic selections and maintained in the peripheral blood. Differences in the mean CDR3 length among different BV subsets were seen throughout lymphocyte development. We also observed that CDR3 was shortened in both CD4 and CD8 thymocytes. Of note, the degrees of the shortening depended on the CD4/CD8 lineage and on use of the BV gene. When expansions of peripheral T cell clones are negligible, no obvious difference was seen between mature thymocytes and peripheral lymphocytes. Thus, the TCRB CDR3 length repertoires are finely tuned in the thymus before the lymphocytes emigrate into the peripheral blood.