Feng Delong, Li Zhaoqiang, Qin Litao, Hao Bingtao
Guangdong Provincial Key Laboratory of Tumor Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, P.R. China.
Genome. 2021 Sep;64(9):821-832. doi: 10.1139/gen-2020-0139. Epub 2021 Feb 22.
T cells recognize the universe of foreign antigens with a diverse repertoire of T cell receptors generated by V(D)J recombination. Special AT-rich binding protein 1 (Satb1) is a chromatin organizer that plays an essential role in T cell development. Previous study has shown that Satb1 regulates the re-induction of recombinase Rag1 and Rag2 in CD4CD8 thymocytes, affecting the secondary rearrangement of the gene. Here, we detected the repertoires of four TCR genes, , , , and , in the adult thymus, and explored the role of the Satb1 in shaping the TCR repertoires. We observed a strong bias in the V and J gene usages of the and repertoires in WT and Satb1-deleted thymocytes. Satb1 deletion had few effects on the V(D)J rearrangement and repertoire of the , , and genes. The repertoire was severely impaired in Satb1-deleted thymocytes, while the primary rearrangement was relatively normal. We also found the CDR3 length of TCRα chain was significantly longer in Satb1-deleted thymocytes, which can be explained by the strong bias of the proximal Jα usage. Our results showed that Satb1 plays an essential role in shaping TCR repertoires in αβ T cells.
T细胞通过V(D)J重排产生的多样化T细胞受体库识别各种外来抗原。特殊富含AT的结合蛋白1(Satb1)是一种染色质组织者,在T细胞发育中起重要作用。先前的研究表明,Satb1调节CD4CD8胸腺细胞中重组酶Rag1和Rag2的重新诱导,影响基因的二次重排。在这里,我们检测了成年胸腺中四个TCR基因( 、 、 、 )的库,并探讨了Satb1在塑造TCR库中的作用。我们观察到野生型和Satb1缺失的胸腺细胞中 和 库的V和J基因使用存在强烈偏差。Satb1缺失对 、 和 基因的V(D)J重排和库影响较小。 在Satb1缺失的胸腺细胞中严重受损,而初级重排相对正常。我们还发现Satb1缺失的胸腺细胞中TCRα链的CDR3长度明显更长,这可以通过近端Jα使用的强烈偏差来解释。我们的结果表明,Satb1在αβ T细胞的TCR库形成中起重要作用。