The role of chromatin organizer Satb1 in shaping TCR repertoire in adult thymus

作者:Feng, Delong; Li, Zhaoqiang; Qin, Litao; Hao, Bingtao*
来源:Genome / National Research Council Canada = Genome / Conseil national de recherches Canada, 2021, 64(9): 821-832.
DOI:10.1139/gen-2020-0139

摘要

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 Satbl regulates the re-induction of recombinase Ragl and Rag2 in CD4(+)CD8(+) thymocytes, affecting the secondary rearrangement of the Tcra gene. Here, we detected the repertoires of four TCR genes, Tcrd, Tcrg, Tcrb, and Tcra, 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 Tcrd and Tcrg repertoires in WT and Satb1-deleted thymocytes. Satb1 deletion had few effects on the V(D)J rearrangement and repertoire of the Tcrg, Tcrd, and Tcrb genes. The Tcra repertoire was severely impaired in Satb1-deleted thymocytes, while the primary rearrangement was relatively normal. We also found the CDR3 length of TCR alpha chain was significantly longer in Satb1-deleted thymocytes, which can be explained by the strong bias of the proximal J alpha usage. Our results showed that Satb1 plays an essential role in shaping TCR repertoires in alpha beta T cells.