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

Hamid R Haghighi,Leah R Read,Shahriar Behboudi,Shayan Sharif,S M Mansour Haeryfar,Derya Unutmaz

doi:10.1371/journal.pone.0007772

Hamid R Haghighi, Leah R Read + Show 4 more

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https://doi.org/10.1371/journal.pone.0007772

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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.

Highlights

Avian influenza virus (AIV) is a type A influenza virus, which belongs to the family of enveloped RNA viruses
Peptide H5246–260, which is located in the HA1 domain of the HA protein, induced greater cell proliferation compared to other peptides within the same pool or compared to controls (Figure 1b), suggesting that H5246–260 was the reacting peptide within this pool
Cell proliferation induced by H5246–260 was not a nonspecific stimulation because cells from sham vaccinated birds did not proliferate in response to this peptide

Summary

Introduction

Avian influenza virus (AIV) is a type A influenza virus, which belongs to the family of enveloped RNA viruses. Birds are the natural hosts of AIV; infection in mammals, including humans can occur by influenza viruses originating from avian hosts [2]. Immunity to influenza viruses is a concerted effort of both innate and adaptive responses. In this regard, T cell-mediated immune responses play a critical role in defense against influenza infection [3]. CD4+ T cells are induced following influenza virus infection and have a central role in immunity via the induction and maintenance of CD8+ T cell memory, and providing help to B cells for antibody production [6,7,8]

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