Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
PLoS One. 2009 Nov 10;4(11):e7772. doi: 10.1371/journal.pone.0007772.
Avian influenza viruses (AIV) of the H5N1 subtype have caused morbidity and mortality in humans. Although some migratory birds constitute the natural reservoir for this virus, chickens may play a role in transmission of the virus to humans. Despite the importance of avian species in transmission of AIV H5N1 to humans, very little is known about host immune system interactions with this virus in these species. The objective of the present study was to identify putative T cell epitopes of the hemagglutinin (HA) antigen of an H5 AIV in chickens. Using an overlapping peptide library covering the HA protein, we identified a 15-mer peptide, H5(246-260,) within the HA1 domain which induced activation of T cells in chickens immunized against the HA antigen of an H5 virus. Furthermore, H5(246-260) epitope was found to be presented by both major histocompatibility complex (MHC) class I and II molecules, leading to activation of CD4+ and CD8+ T cell subsets, marked by proliferation and expression of interferon (IFN)-gamma by both of these cell subsets as well as the expression of granzyme A by CD8+ T cells. This is the first report of a T cell epitope of AIV recognized by chicken T cells. Furthermore, this study extends the previous finding of the existence of dual-specific epitopes in other species to chickens. Taken together, these results elucidate some of the mechanisms of immune response to AIV in chickens and provide a platform for creation of rational vaccines against AIV in this species.
禽流感病毒(AIV)的 H5N1 亚型已导致人类发病和死亡。尽管一些候鸟是该病毒的天然宿主,但鸡可能在病毒传播给人类方面发挥作用。尽管禽类在将 AIV H5N1 传播给人类方面具有重要作用,但人们对这些物种中宿主免疫系统与该病毒相互作用的了解甚少。本研究的目的是鉴定 H5 AIV 血凝素(HA)抗原中的推定 T 细胞表位。使用覆盖 HA 蛋白的重叠肽文库,我们在 HA1 结构域内鉴定出一个 15 肽,H5(246-260,),该肽在针对 H5 病毒 HA 抗原免疫的鸡中诱导 T 细胞激活。此外,发现 H5(246-260) 表位由主要组织相容性复合体 (MHC) 类 I 和 II 分子呈递,导致 CD4+和 CD8+T 细胞亚群激活,这两个细胞亚群的增殖和干扰素 (IFN)-γ表达以及 CD8+T 细胞的颗粒酶 A 表达均可证明这一点。这是首次报道鸡 T 细胞识别的 AIV T 细胞表位。此外,这项研究将其他物种中存在双特异性表位的先前发现扩展到了鸡。总之,这些结果阐明了鸡对 AIV 免疫反应的一些机制,并为在该物种中针对 AIV 开发合理疫苗提供了平台。