Absence of ZAP-70 prevents signaling through the antigen receptor on peripheral blood T cells but not on thymocytes.-猫眼课题宝

没有ZAP-70可阻止通过外周血T细胞上的抗原受体信号传导，但不能在胸腺细胞上发出信号。

DOI：

10.1084/jem.182.4.1057

发表时间：

1995-10-01

期刊：

JOURNAL OF EXPERIMENTAL MEDICINE

影响因子：

15.3

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Gelfand, Erwin W.;Weinberg, Kenneth;Mazer, Bruce D.;Kadlecek, Theresa A.;Weiss, Arthur

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192291/?report=classic

最近，一种严重的联合免疫缺陷综合征，伴有 CD8+ 外周 T 细胞缺乏和外周 CD4+ T 细胞 TCR 信号转导缺陷，与 ZAP-70 突变有关。由于 TCR 信号传导在导致成熟 CD4（和 CD8）T 细胞的发育决策中是必需的，因此在这些患者中表达不能传导信号的 TCR 的外周 CD4+ T 细胞的存在是矛盾的。在这里，我们证明来自 ZAP-70 缺陷患者的胸腺细胞（而非外周 T 细胞）上的 TCR 能够发出信号。此外，来自该患者的胸腺细胞系上的TCR可以发出信号，同源激酶Syk以高水平存在，并且在TCR刺激后被酪氨酸磷酸化。因此，Syk 可以补偿 ZAP-70 的损失，并解释 ZAP-70 缺陷患者中至少一部分 T 细胞 (CD4+) 的胸腺选择。

Recently, a severe combined immunodeficiency syndrome with a deficiency of CD8+ peripheral T cells and a TCR signal transduction defect in peripheral CD4+ T cells was associated with mutations in ZAP-70. Since TCR signaling is required in developmental decisions resulting in mature CD4 (and CD8) T cells, the presence of peripheral CD4+ T cells expressing TCRs incapable of signaling in these patients is paradoxical. Here, we show that the TCRs on thymocytes, but not peripheral T cells, from a ZAP-70-deficient patient are capable of signaling. Moreover, the TCR on a thymocyte line derived from this patient can signal, and the homologous kinase Syk is present at high levels and is tyrosine phosphorylated after TCR stimulation. Thus, Syk may compensate for the loss of ZAP-70 and account for the thymic selection of at least a subset of T cells (CD4+) in ZAP-70-deficient patients.