Li Jiaqi, Liang Wei, Li Kang, Jiao Xinying, Ai Kete, Zhang Yu, Wei Xiumei, Yang Jialong
State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Dev Comp Immunol. 2021 Nov;124:104177. doi: 10.1016/j.dci.2021.104177. Epub 2021 Jun 18.
ZAP70 is essential for initiating the early events of T-cell antigen receptor (TCR) signaling cascade to ensure proper T cell activation and function. However, whether this molecule takes part in the T cell immune response of early vertebrates remains unclear. In the present study, using a teleost model Nile tilapia (Oreochromis niloticus), we investigated the potential involvement of ZAP70 in the T cell activation and adaptive immunity of fish species. Both primary and tertiary structures of O. niloticus ZAP70 (On-ZAP70) are highly conserved with those from other vertebrates. On-ZAP70 protein was widely expressed in lymphoid tissues, and with the highest level in thymus. Once Nile tilapia was infected by Aeromonas hydrophila, mRNA of On-ZAP70 in spleen lymphocytes was induced on day 5 and 8 after infection; meanwhile, phosphorylation of On-ZAP70 was also enhanced, suggesting that On-ZAP70 potentially participated in primary adaptive immune response of Nile tilapia. Furthermore, the frequency of ZAP70 positive lymphocytes was increased during the anti-bacterial adaptive immune response. More importantly, when spleen lymphocytes were activated by T cell specific mitogen PHA, a dramatical augment of On-ZAP70 could be observed at transcription, phosphorylation and cellular level, indicating the involvement of this molecule in T cells activation of Nile tilapia. Altogether, our results demonstrated that ZAP70 activation is an early event of T cell immunity that involved in the anti-bacterial adaptive immune response of Nile tilapia, and thus provided a new evidence to understand the evolution of the lymphocyte-mediated adaptive immunity.
ZAP70对于启动T细胞抗原受体(TCR)信号级联反应的早期事件至关重要,以确保T细胞的正常激活和功能。然而,该分子是否参与早期脊椎动物的T细胞免疫反应仍不清楚。在本研究中,我们使用硬骨鱼模型尼罗罗非鱼(Oreochromis niloticus),研究了ZAP70在鱼类T细胞激活和适应性免疫中的潜在作用。尼罗罗非鱼ZAP70(On-ZAP70)的一级和三级结构与其他脊椎动物的高度保守。On-ZAP70蛋白在淋巴组织中广泛表达,在胸腺中的表达水平最高。尼罗罗非鱼一旦被嗜水气单胞菌感染,感染后第5天和第8天脾脏淋巴细胞中On-ZAP70的mRNA被诱导;同时,On-ZAP70的磷酸化也增强,表明On-ZAP70可能参与尼罗罗非鱼的初级适应性免疫反应。此外,在抗菌适应性免疫反应过程中,ZAP70阳性淋巴细胞的频率增加。更重要的是,当脾脏淋巴细胞被T细胞特异性丝裂原PHA激活时,在转录、磷酸化和细胞水平上可观察到On-ZAP70显著增加,表明该分子参与尼罗罗非鱼T细胞的激活。总之,我们的结果表明,ZAP70激活是T细胞免疫的早期事件,参与尼罗罗非鱼的抗菌适应性免疫反应,从而为理解淋巴细胞介导的适应性免疫的进化提供了新的证据。