Category: 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.
Fransenio Clark– Graduate Student, University of Massachusetts Medical School
Rabinarayan Mishra– Instructor, University of Massachusetts Medical School
Anna Gil– Instructor, University of Massachusetts Medical School
Nuray Aslan– Post-doctoral Fellow, University of Massachusetts
Katherine Luzuriaga– Director and PI of the University of Massachusetts Center for Clinical and Translational Science, University of Massachusetts Medical School