T细胞受体
拉格2
生物
基因重排
否定选择
CD8型
等位基因排除
重组激活基因
细胞毒性T细胞
基因
分子生物学
细胞生物学
谱系(遗传)
T细胞
遗传学
CD3型
抗原
重组
免疫系统
基因组
作者
Edward P. Chen,Patrick M. Brauer,Elisa Martinez,Xiaotian Huang,Ning Yu,Michele K. Anderson,Yan Li,Juan Carlos Zúñiga-Pflücker
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2021-05-03
卷期号:206 (10): 2271-2276
被引量:4
标识
DOI:10.4049/jimmunol.2100141
摘要
T cell development is predicated on the successful rearrangement of the TCR gene loci, which encode for Ag-specific receptors. Recombination-activating gene (RAG) 2 is required for TCR gene rearrangements, which occur during specific stages of T cell development. In this study, we differentiated human pluripotent stem cells with a CRISPR/Cas9-directed deletion of the RAG2 gene (RAG2-KO) to elucidate the requirement for the TCR β-chain in mediating β-selection during human T cell development. In stark contrast to mice, human RAG2-KO T lineage progenitors progressed to the CD4+CD8+ double-positive (DP) stage in the absence of TCRβ rearrangements. Nonetheless, RAG2-KO DPs retrovirally transduced to express a rearranged TCR β-chain showed increased survival and proliferation as compared with control-transduced RAG2-KO DPs. Furthermore, transcriptomic analysis showed that TCRβ- and control-transduced RAG2-KO DPs differed in gene pathways related to survival and proliferation. Our results provide important insights as to the distinct requirement for the TCR β-chain during human T cell development.
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