| Rational vaccine design requires detailed knowledge on the processes guiding T cell differentiation into the functional effector and memory subset that is most effective in clearing the infection. While multiple T cell subsets have been identified, it remains largely elusive how they arise. My aim is to investigate how these effector/memory subsets are formed, by assessing the link between T cell activation and subsequent T cell differentiation in vivo. In the first part of the proposed project I will investigate how the T cell receptor (TCR) affinity for antigen shapes the dynamic interactions between T cells and antigen-presenting dendritic cells (DCs) during T cell activation, and how this influences subsequent T cell differentiation. The duration of DC-T cell contacts will be determined by multi-photon intra-vital microscopy shortly after vaccination. In the second part I aim to establish which DC-T cell contacts lead to signaling through the TCR. This will be achieved by imaging changes in sub-cellular localization of fluorescent molecules, which report on the occurrence of TCR signaling. The results will provide insights in the development of effector and memory T cells |
