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

基因組織檢測公司示例

閱讀腫瘤基因解碼如何提升基因檢測的可能知悉《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。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調了基因信息檢測與分析的重要性。

腫瘤基因檢測及靶向藥物治療研究關鍵詞：

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

腫瘤治療檢測基因臨床應用結果

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

腫瘤發(fā)生與革命國際數(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.