Abstract

MHC class II molecules present antigenic fragments to CD4 T cells and thus control a plethora of immune responses. The cell biology of MHC class II is also of interest as it enters the endosomal pathway to acquire antigenic fragments before moving to the plasma membrane for presentation.

We will describe two aspect related to the transport of MHC class II molecules. This involves the Rab7-RILP associated dynein motor and the mode of control of late endosomal vesicle fusion. We show how these processes are controlled by proteins on another compartments (the ER) and how this is finally controlled by cholesterol. In addition, we aimed to identify processes controlling MHC class II transport in dendritic cells where they are surface deposited following activation. We have performed an siRNA screen and –after secondary screens and expression profiling- predicted a number of candidate proteins involved in the control of MHC class II transport in dendritic cells. We show how this is used to define new pathways that explain how MHC class II is controlled involving a new GTPase ARF7 and the myosin motor 1E.

Integrating high content screens with imaging, protein chemistry and other techniques allows definition of new pathways controlling MHC class II molecules.