?d T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection

Dong, Peng; Ju, Xiangwu; Yan, Yiwu; Zhang, Siya; Cai, Menghua; Wang, Huaishan; Chen, Hui; Hu, Yu; Cui, Lianxian; Zhang, Jianmin; He, Wei

To further determine the molecular mechanism underlying γδ T cell activation by rH5HA trimer stimulation, we first analyzed the expression of sialic acid receptors, which is a major determinant of the cellular tropism of the influenza virus, on the surface of γδ T cells. As previously reported, both α-2,3 and α-2,6 sialic acid receptors could be detected on γδ T cells (25) . The expression level of α-2,6 sialic acid receptors was higher than that of α-2,3 sialic acid receptors ( Figure 5A ). In addition, both HAF and HA-his proteins bound directly to the surface of γδ T cells, and HAF proteins had the higher binding ability. However, neither HAF nor HA-his proteins could bind to the surface of γδ T cells after neuraminidase digestion (Figures 5B,C) . Furthermore, the ability of HAF proteins to stimulate IFN-γ production disappeared after neuraminidase digestion (Figure 5D) , indicating a requirement of sialic acid receptors for the HAF-induced γδ T cell activation. In addition, when HAF proteins were treated with endoglycosidase H (Endo H), only very little production of IFN-γ by γδ T cells could be detected (Figures 5E,F) , suggesting that the glycosylation of HA also plays an important role in HAF-induced γδ T cell activation.