Enterovirus 71 capsid protein VP1 specifically recognizes and activates CD4+ T cell immune activation in children with hand, foot and mouth disease

Abstract

Objective To investigate the characteristics of interferon-γ(IFN-γ) response induced by enterovirus 71 (EV71) capsid protein VP1 in peripheral blood T lymphocytes of children with EV71 infection. Methods From September 2010 to December 2011, a total of 31 patients with hand, foot and mouth disease (HFMD) infected with EV71 were collected from the Second Affiliated Hospital of Medical College of Xi’an Jiaotong University and Xi’an Children’s Hospital. According to the clinical features, 31 cases were divided into three groups: acute infection group (16 cases), clinical convalescence group (9 cases) and one month after recovery of infection group (6 cases), in addition, 10 healthy children were selected as control group. Total of 36 overlapping peptides of EV71 capsid protein VP1 were synthesized by overlapping peptide technique as antigens. The immunological responses of EV71 VP1 specific CD4+T and CD8+T cells were detected by IFN-γenzyme-linked immunoblot assay (ELISPOT) and magnetic cell sorting (MACs) in vitro. Results In the acute infection group, 4 cases (25%) had T cell immune response to VP1 protein, 5 cases (56%) in the clinical convalescence group had T cell immune response to VP1 protein. The strength of T-cell responses in clinical convalescence group had the strongest, significantly higher than acute infection group (Z=-2.042,P= 0.041), and one month after recovery of infection group (Z=-2.105,P = 0.035) and control group (Z=-2.633,P = 0.008), with significant differences. The T cell immune response was not detected in the control group and one month after recovery of infection group. The results suggested that the frequency of VP1 protein recognition (the number of cases) disappeared with the disappearance of clinical symptoms and signs in children with EV71 infection. The cellular immune response induced by VP1 protein was dominated by specific CD4+T cells. Eight CD4+T cell epitopes of EV71 VP1 protein region were identified. Conclusions There was a specific T cell response to VP1 protein in children with EV71 infection, and the specific CD4+T cells were dominant. The CD4+T cell epitopes of VP1 protein were identified in EV71 infected children. It is helpful to elucidate the cellular immunopathogenesis of EV71 infection. Key words: Enterovirus 71; T cell-mediated immunity; Capsid protein VP1; Enzyme-linked immunospot assays; T cell Epitope