On Friday, May 23rd, 2008 Anna Keller will defend her thesis titled “The role of CD 70/CD27 interactions at the dendritic cell/T cell interface” in order to obtain the doctorate degree from the University of Amsterdam.
Her promoter is professor Jannie Borst.
Functioning of the immune system is based on complicated mechanisms that allow for recognition and removal of pathogenic intruders, without damaging the ‘self’ tissue.
These processes are controlled by dendritic cells that can induce either immune attack or immune tolerance. Immune attack is initiated when naïve T cells are primed by antigen presentation in the context of major histocompatibility complex (MHC) molecules on dendritic cells.
Lifespan and functional characteristics of primed T cells are determined by several additional signals offered by dendritic cells. CD70 is one of such co-stimulatory molecules that upon binding of its receptor CD27, promotes effector T cell accumulation and formation of T cell memory. In this thesis I studied the impact on T cell fate of the CD70/CD27 interactions at the interface between a dendritic cell and a T cell.
Anna Keller has demonstrated that intracellular transport of CD70 in dendritic cells is intimately coupled to the transport of MHC class II molecules and that both molecules are simultaneously delivered to the contact point between a dendritic cell and a T cell. This allows for the coordination of antigen presentation and T cell co-stimulation via CD27, resulting in optimal stimulation of naïve T cells. She further found that the invariant chain, known until now as a chaperone of MHC class II molecules, plays the function of chaperone also for CD70.
This unexpected role of invariant chain highlighted the importance of the tight regulation of timing and level of CD70 expression. Indeed, a small increase in surface CD70 in the absence of invariant chain in dendritic cells resulted in the dramatically enhanced survival of primed T cells. Additionally, she showed that the mere delivery of costimulation via CD27 is sufficient to break tolerance and induce protective immunity instead. This suggests that the employment of CD27/CD70 costimulatory axis at the dendritic cell/T cell interface is crucial for T cell priming and memory formation and holds promise for dendritic cell-based anti-tumor immunotherapy.
Proposition 7 which accompanies the thesis states: Chance favors only the prepared mind (Louis Pasteur). That’s why perseverance is worth the effort.
The thesis defence is open to the public and will take place in the Agnietenkapel, Amsterdam, at 12.00 hours.