Antigen presentation by MHCII in cross-presenting dendritic cells. – Help2Kill

The activation of long-lived cytotoxic CD8+ T cell responses is central to protective immunity against viruses and tumours. This type of immune response is activated by antigenic presentation on MHCI at the surface of type 1 DCs (DC1s) after the phagocytosis of dead cells carrying antigen. This process is termed as cross-presentation. Efficient activation of CD8+ T cells also requires antigenic presentation by MHCII to CD4+ T cells. Genetic evidences and intra-vital imaging studies support the notion that the same cross-presenting DCs also perform MHCII presentation. Therefore, the coordination of both MHCI and MHCII presentation is crucial for immune responses but remains ill ill-understood.

Specifically, we intend:

1. To assess simultaneously the dynamics of MHCII and MHCI trafficking and presentation/cross-presentation in phagocytic DC1s.

2. To identify key DC1-associated genes encoding for traffic regulators supporting MHCII presentation.

3. To assess the contribution of DC1-associated MHCII regulators in the induction of long-lived CD8+ T cells responses in vivo using DC1-specific gene targeting.