Deep sequencing of the human TCRγ and TCRβ repertoires suggests that TCRβ rearranges after αβ and γδ T cell commitment.
Deep sequencing of the human TCRγ and TCRβ repertoires suggests that TCRβ rearranges after αβ and γδ T cell commitment.
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DOI：
10.1126/scitranslmed.3002536
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发表时间：
2011-07-06
影响因子：
17.1
通讯作者：
Robins H
中科院分区：
文献类型：
--
作者：
Sherwood AM;Desmarais C;Livingston RJ;Andriesen J;Haussler M;Carlson CS;Robins H
T淋巴细胞的两个主要谱系来自于人类胸腺中的多潜能前体细胞。血液中最常见的T细胞是αβT细胞，它通过人类白细胞抗原分子与细胞表面的抗原肽结合。人们对HLAT细胞的了解要少得多，这种细胞不结合γδ：多肽复合体，在肠粘膜中更普遍。对于这两个谱系，它们识别不同抗原的能力是由其表面重排的Y-样受体介导的，T细胞受体(T细胞受体)由α和β链(αβT细胞)或γ和δ链(γδT细胞)组成。从前体向这两个谱系承诺的典型模型假设，γ，δ和β链在向αβ或γδT细胞承诺之前重新排列。要更好地理解γδT细胞的作用，关键的一步是弄清楚发育过程。为了测试标准模型和理解γδTCR谱，我们使用高通量测序技术对来自三个无关个体的几百万条TCRTCRDNA和TCRTCRDNA链进行了分类，分别来自于外周血中的γ和βT细胞。几乎所有采样的αβ和γδT细胞都有TCRγ序列重排。虽然采样的αβT细胞具有不同的重排TCRβ链，但外周血中只有不到10%的γδT细胞具有重排的TCRβ链。我们的数据表明，TcRγ在所有T淋巴细胞中重排，与T细胞谱系承诺之前的TcRγ重排一致，而TcRβ位点的重排受到限制，发生在T细胞前体向αβT细胞谱系承诺之后。这一结果解释了T细胞白血病和淋巴瘤中的难题，即TcRγ几乎总是重排，而TcRβ只在一小部分癌症中重排。随着TCRs的高通量测序被转化到临床上用于监测白血病/淋巴瘤的最小残留，我们的数据表明测序目标需要是TCRTCRs。
The two main lineages of T lymphocytes develop from multi potent precursors in the human thymus. The most common type in blood are αβ T cells, which bind to antigenic peptides displayed on the surface of cells by human leukocyte antigen (HLA) molecules. Far less well understood are γδ T cells, which do not bind HLA: peptide complexes and are more prevalent in the gut mucosa. For both lineages, their ability to recognize a diverse array of antigens is mediated by a rearranged Y-like receptor on their surface, the T cell receptor (TCR), composed and of an α and β chain for αβ T cells or a γ and δ chain for γδ T cells. The canonical model for commitment from the precursor to one these two lineages assumes that γ, δ, and β chains rearrange prior to commitment to αβ or γδ T cells. A crucial step towards better understanding the role of γδ T cells is to work out the developmental process. To test the standard model and to understand the γδ TCR repertoire, we use high-throughput sequencing to catalog millions of TCRγ and TCRβ chains from peripheral blood αβ and γδ T cells, from three unrelated individuals. Almost all sampled αβ and γδ T cells have rearranged TCRγ sequences. While sampled αβ T cells have a diverse repertoire of rearranged TCRβ chains, less than 10% of γδ T cells in peripheral blood have a rearranged TCRβ chain. Our data indicate that TCRγ rearranges in all T lymphocytes, consistent with TCRγ rearranging prior to T cell lineage commitment, while rearrangement of the TCRβ locus is restricted, and occurs after T cell precursors commit to the αβ T cell lineage. This result explains the conundrum in T cell leukemia and lymphoma that TCRγ is almost always rearranged and TCRβ is only rearranged in a subset of cancers. As high-throughput sequencing of TCRs is translated into the clinic for monitoring minimal residual for leukemia/lymphoma, our data suggests the sequencing target needs to be TCR γ.
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影响因子：
4.4
作者：
Joachims, ML;Chain, JL;Thompson, LF
通讯作者：
Thompson, LF
影响因子：
7.8
作者：
Meyer C;Zeng X;Chien YH
通讯作者：
Chien YH
影响因子：
5.8
作者：
Hebbeler, Andrew M.;Cairo, Cristiana;Pauza, C. David
通讯作者：
Pauza, C. David
影响因子：
15.3
作者：
DELIBERO, G;CASORATI, G;LANZAVECCHIA, A
通讯作者：
LANZAVECCHIA, A
DOI：
10.1084/jem.20042524
发表时间：
2005-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dik WA;Pike-Overzet K;Weerkamp F;de Ridder D;de Haas EF;Baert MR;van der Spek P;Koster EE;Reinders MJ;van Dongen JJ;Langerak AW;Staal FJ
通讯作者：
Staal FJ