Cross-reactive CD8 T-cell responses in human viral infections

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

ABSTRACT 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 that infects millions per year, and Epstein Barr Virus (EBV), a persistent virus which resides in 95% of the population. Using EBV seropositive, HLA-A2+, teenage (18 years old) and middle-age donors (30-50 years old), this study demonstrates memory inflation to EBV. CD8+ memory T cell responses to recurrent and persistent viruses change as an individual ages. We used tetramers and dextramers to study both cross-reactive and antigen specific cells that are present in whole blood and proliferate in response to stimulation with immuno-dominant epitopes of influenza and EBV. While the phenomenon of memory inflation has been described in the literature for another persistent virus, cytomegalovirus (CMV), our data suggests memory inflation to EBV occurs in middle- aged donors. These data also suggests a role for cross-reactive responses, which differs between teenage and middle-aged donors and a narrowing of the T cell receptor (TCR) V beta repertoire occurs as an individual increases in age. 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.