Harnessing CD8 T cell immunity to fight viral infection

The importance of T cell-mediated protection in virus-induced disease has become widely appreciated since the COVID-19 pandemic. Memory CD8 T cells play a key role in the protection from severe COVID-19.

Memory CD8 T cell reactivity has furthermore persisted against viral variants that have escaped antibody neutralization.

Consequently, there is a need for vaccines that induce potent CD8 T cell memory in addition to neutralizing antibodies against viral infections.

Two important factors that determine the potency of anti-viral CD8 T cell responses are the size of the CD8 T cell response, and the functional properties of the T cells.

Which exact T cell properties are most relevant for protection may depend on the virus.This project will provide a fundamental knowledge base to direct vaccine design against SARS-CoV-2 and other known and emerging viral diseases towards inducing high numbers of CD8 T cells with specific functional properties.We will investigate what factors modulate CD8 T cell response size or CD8 T cell function in response to vaccination and acute viral infection in mice.

Given that both response size and T cell functional fate are highly divergent between individual T cell clones, the relationship between T cell clonal expansion and T cell function needs to be studied on a clonal level.

To study these processes in a T cell receptor affinity-controlled manner, we will make use of the high-throughput single-cell fate mapping technology ´cellular barcoding´.