Contrasting Epstein-Barr virus-specific cytotoxic T cell responses to HLA A2-restricted epitopes in humans and HLA transgenic mice: implications for vaccine design

This study investigates the hierarchy of cytotoxic T cell (CTL) responses t o twelve HLA AZ-restricted epitopes from the latent, lytic and structural p roteins of Epstein-Barr virus (EBV) in acute infectious mononucleosis and i n healthy seropositive donors and the relative immunogenecity of these epit opes in transgenic mice. Responses to the lytic epitope were uniformly stro ng in all healthy seropositive individuals and acute infectious mononucleos is donors while moderate or low responses were observed to the latent and s tructural epitopes. respectively in both groups studied. In contrast, when HLA A2/Kb transgenic mice were immunised with these peptide epitopes, CTL r esponses were observed to all epitopes with a maximal response to the epito pes within the structural proteins and low to moderate responses to the lat ent epitopes. This hierarchy of CTL responses in mice was also reflected in an MHC stabilisation analysis. These contrasting CTL responses in humans f ollowing natural infection compared to the immunogenicity of these epitopes and their ability to stabilise MHC mag; need to be considered when designi ng an EBV vaccine. (C) 2001 Elsevier Science Ltd. All rights reserved.