【佳學(xué)基因靶向藥物基因檢測(cè)】LAT 銜接子第六個(gè)酪氨酸前甘氨酸殘基的突變嚴(yán)重改變了 T 細(xì)胞的發(fā)育和激活

基因組織檢測(cè)公司示例

閱讀腫瘤基因解碼如何提升基因檢測(cè)的可能知悉《Front Immunol》在?2022 Dec 7;13:1054920.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由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。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤基因檢測(cè)及靶向藥物治療研究關(guān)鍵詞：

T細(xì)胞, T細(xì)胞發(fā)育, T細(xì)胞記憶, TCR（T 細(xì)胞受體）,無活力,激活 T 細(xì)胞的接頭。

腫瘤治療檢測(cè)基因臨床應(yīng)用結(jié)果

LAT 跨膜適配器對(duì)于轉(zhuǎn)導(dǎo)由 TCR 觸發(fā)的細(xì)胞內(nèi)信號(hào)至關(guān)重要。其四個(gè) C 末端酪氨酸殘基（小鼠 LAT 中的 136、175、195 和 235）的磷酸化會(huì)招募幾種蛋白質(zhì)，從而導(dǎo)致 LAT 信號(hào)體的組裝。在這些酪氨酸殘基中，位于小鼠 LAT 136 位的酪氨酸殘基對(duì) T 細(xì)胞的發(fā)育和激活起著至關(guān)重要的作用。由于在第 135 位發(fā)現(xiàn)了一個(gè)保守的甘氨酸殘基，與其他三個(gè) C 末端酪氨酸相比，該殘基的磷酸化動(dòng)力學(xué)被延遲。該甘氨酸突變?yōu)樘於彼釟埢ū硎緸?LATG135D）增加了 TCR 信號(hào)并改變了抗原識(shí)別人 Jurkat T 細(xì)胞和離體小鼠 T 細(xì)胞。在這里，使用 LATG135D 敲入小鼠品系，我們發(fā)現(xiàn) LATG135D 突變改變胸腺發(fā)育，導(dǎo)致 CD4+CD8+ 雙陽性細(xì)胞百分比增加，以及 CD4+ 和 CD8+ 單陽性細(xì)胞百分比降低。有趣的是，即使在雜合子狀態(tài)下，LATG135D 突變也會(huì)改變胸腺發(fā)育。在外周，LATG135D 突變降低了 CD8+ T 細(xì)胞的百分比，并導(dǎo)致 γδ T 細(xì)胞少量增加。值得注意的是，LATG135D 突變顯著增加了中央記憶 CD8+ T 細(xì)胞的百分比。賊后，對(duì) T 淋巴細(xì)胞增殖和激活的分析表明，來自突變小鼠的 T 細(xì)胞反應(yīng)增強(qiáng)。總而言之，我們的結(jié)果強(qiáng)化了 LAT Tyr136 之前的殘基構(gòu)成 T 細(xì)胞發(fā)育和激活的關(guān)鍵檢查點(diǎn)的觀點(diǎn)。 T細(xì)胞發(fā)育； T細(xì)胞記憶； TCR（T 細(xì)胞受體）；無活力；激活 T 細(xì)胞的接頭。

腫瘤發(fā)生與革命國(guó)際數(shù)據(jù)庫描述：

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.