?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

Here, we further confirmed that the expression level of α-2,6 sialic acid receptors was higher than that of α-2,3 sialic acid receptors; this result is consistent with a previous report that α-2,6 sialic acid is dominant on epithelial cells in the human nasal mucosa (38) . Both the HAF and HA-his proteins bound directly to the surface of γδ T cells, and HAF proteins were observed to have the higher binding ability, consistent with the agglutination ability of their γδ T cells. Furthermore, we confirmed that the activation of γδ T cells induced by HA trimers was dependent on sialic acid receptors; HA trimers could not bind to the surface of γδ T cells, and the stimulation of IFN-γ production by HA trimers disappeared after neuraminidase digestion. HA from human-derived viruses preferentially recognizes α-2,6 sialic acid receptors, whereas HA from avian viruses preferentially recognizes α-2,3 sialic acid receptors (38) . Our results confirm that although the expression level of α-2,3 sialic acid receptors is lower than that of α-2,6 sialic acid receptors, the expression is sufficient to induce γδ T cell activation. Glycosylation plays a critical role in HA cleavage, structural stability and pathogenicity in HPAI H5N1 virus infection (39) . In our study, we found that HA glycosylation plays an important role in γδ T cell activation; the production of IFN-γ by γδ T cells was nearly absent after the treatment of HAF proteins with Endo H.