【广东会GDH基因靶向药物基因检测】LAT 衔接子第六个酪氨酸前甘氨酸残基的突变严重改变了 T 细胞的发育和激活
基因组织检测公司示例
阅读肿瘤基因解码如何提升基因检测的可能知悉《Front Immunol》在 2022 Dec 7;13:1054920.发表了一篇题目为《》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Mikel M Arbulo-Echevarria, Inmaculada Vico-Barranco, Fanghui Zhang, Luis M Fernandez-Aguilar, Martyna Chotomska, Isaac Narbona-Sánchez, Lichen Zhang, Bernard Malissen, Yinming Liang, Enrique Aguado等完成。促进了肿瘤的正确治疗与个性化用药的发展,进一步强调了基因信息检测与分析的重要性。
肿瘤基因检测及靶向药物治疗研究关键词:
T细胞, T细胞发育, T细胞记忆, TCR(T 细胞受体),无活力,激活 T 细胞的接头。
肿瘤治疗检测基因临床应用结果
LAT 跨膜适配器对于转导由 TCR 触发的细胞内信号至关重要。其四个 C 末端酪氨酸残基(小鼠 LAT 中的 136、175、195 和 235)的磷酸化会招募几种蛋白质,从而导致 LAT 信号体的组装。在这些酪氨酸残基中,位于小鼠 LAT 136 位的酪氨酸残基对 T 细胞的发育和激活起着至关重要的作用。由于在第 135 位发现了一个保守的甘氨酸残基,与其他三个 C 末端酪氨酸相比,该残基的磷酸化动力学被延迟。该甘氨酸突变为天冬氨酸残基(表示为 LATG135D)增加了 TCR 信号并改变了抗原识别人 Jurkat T 细胞和离体小鼠 T 细胞。在这里,使用 LATG135D 敲入小鼠品系,我们发现 LATG135D 突变改变胸腺发育,导致 CD4+CD8+ 双阳性细胞百分比增加,以及 CD4+ 和 CD8+ 单阳性细胞百分比降低。有趣的是,即使在杂合子状态下,LATG135D 突变也会改变胸腺发育。在外周,LATG135D 突变降低了 CD8+ T 细胞的百分比,并导致 γδ T 细胞少量增加。值得注意的是,LATG135D 突变显着增加了中央记忆 CD8+ T 细胞的百分比。贼后,对 T 淋巴细胞增殖和激活的分析表明,来自突变小鼠的 T 细胞反应增强。总而言之,我们的结果强化了 LAT Tyr136 之前的残基构成 T 细胞发育和激活的关键检查点的观点。 T细胞发育; T细胞记忆; TCR(T 细胞受体);无活力;激活 T 细胞的接头。
肿瘤发生与革命国际数据库描述:
The LAT transmembrane adaptor is essential to transduce intracellular signals triggered by the TCR. Phosphorylation of its four C-terminal tyrosine residues (136, 175, 195, and 235 in mouse LAT) recruits several proteins resulting in the assembly of the LAT signalosome. Among those tyrosine residues, the one found at position 136 of mouse LAT plays a critical role for T cell development and activation. The kinetics of phosphorylation of this residue is delayed as compared to the three other C-terminal tyrosines due to a conserved glycine residue found at position 135. Mutation of this glycine into an aspartate residue (denoted LATG135D) increased TCR signaling and altered antigen recognition in human Jurkat T cells and ex vivo mouse T cells. Here, using a strain of LATG135D knockin mice, we showed that the LATG135D mutation modifies thymic development, causing an increase in the percentage of CD4+CD8+ double-positive cells, and a reduction in the percentage of CD4+ and CD8+ single-positive cells. Interestingly, the LATG135D mutation alters thymic development even in a heterozygous state. In the periphery, the LATG135D mutation reduces the percentage of CD8+ T cells and results in a small increment of γδ T cells. Remarkably, the LATG135D mutation dramatically increases the percentage of central memory CD8+ T cells. Finally, analysis of the proliferation and activation of T lymphocytes shows increased responses of T cells from mutant mice. Altogether, our results reinforce the view that the residue preceding Tyr136 of LAT constitutes a crucial checkpoint in T cell development and activation.Keywords: T cell; T cell development; T cell memory; TCR (T cell receptor); anergy; linker for activation of T cell.
(责任编辑:广东会GDH基因)