Immunity & infection
CD8+ memory T cells are generated during primary infection with intracellular pathogens, such as viruses. These cells play an important role in the protection of the host upon re-infection with the same pathogen.In this study, we compare CD8+ memory T cell responses to both influenza A virus (IAV), a recurrent virus and Epstein Barr Virus (EBV), a persistent virus. Using EBV seropositive, HLA-A2+, young adult (18-20 years) and elderly (>65 years) donors, this study demonstrates that CD8+ memory T cell responses to both recurrent and persistent viruses co-evolve as an individual ages. Tetramer-staining was used to study both cross-reactive and antigen-specific cells that were present in peripheral blood and proliferated in response to stimulation with immuno-dominant epitopes of IAV and EBV. There were significant differences in IAV-M158, EBV-BMLF1280, and EBV-BRLF1190 Vβ usage as individuals age.Young and elderly adults had different cross-reactive patterns. Young adults had increased opportunity for cross-reactivity due to increased TCR diversity resulting in increased numbers of shared Vb families amongst all 3 epitopes.Elderly donors had evidence of increased focusing on cross-reactivity with a more narrow repertoire.Tracking 3 donors over 10-20 years showed that the changes in TcR repertoire of IAV-M1, EBV-BMLF1 and -BRLF1-specific responses during acute IAV infection may be mediated by TcR crossreactivity and may lead to altered T cell activation and function.This study further emphasizes the complexity of human T cell responses to viruses and the need for a better understanding of human T cell responses in order to design successful T cell inducing vaccines.