Research Article: Identification of a Dual-Specific T Cell Epitope of the Hemagglutinin Antigen of an H5 Avian Influenza Virus in Chickens

Date Published: November 10, 2009

Publisher: Public Library of Science

Author(s): Hamid R. Haghighi, Leah R. Read, S. M. Mansour Haeryfar, Shahriar Behboudi, Shayan Sharif, Derya Unutmaz.

Abstract: 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, H5246–260, within the HA1 domain which induced activation of T cells in chickens immunized against the HA antigen of an H5 virus. Furthermore, H5246–260 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)-γ 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.

Partial Text: Avian influenza virus (AIV) is a type A influenza virus, which belongs to the family of enveloped RNA viruses. AIV genome encodes 11 proteins, among which hemagglutinin (HA) and neuraminidase (NA), are two surface antigens that are used to classify influenza viruses [1]. Birds are the natural hosts of AIV; however, infection in mammals, including humans can also occur by influenza viruses originating from avian hosts [2].

The main objective of the present study was to identify T cell epitopes of the HA antigen of an H5 AIV in chickens. Using a peptide library covering the full length of the HA protein, we found a 15-mer peptide that was able to induce T cell proliferation and IFN-gamma expression in chickens immunized with a fowlpox virus-based vaccine expressing the H5 protein. Our data suggest that this peptide was presented by both MHC class I and II molecules, leading to activation of CD4+ and CD8+ T cell subsets. The importance of these findings is two fold. First, this is the first study to identify an immunodominant T cell epitope of AIV in chickens and, second, the H5 epitope identified here has the capacity to stimulate both T cell subsets. Vaccination with dual-specific epitopes may be more efficacious than a mixture of CTL and Th cell epitopes, as they could allow CD4+ and CD8+ cells to interact with the same APC, thereby improving communication between cells [33].



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