The processing and presentation of antigenic peptides on MHC class II molecules are an important prerequisite of the immune system to be able to defend against invading pathogens, monitor self-reactivity, and fight tumour cells. These delicate antigen presentation pathways regulating the generation of MHC class II peptides require a multitude of different compartments and proteases within the cell, which need to be clarified. In the proposed project, confocal live cell imaging will be used to investigate the involvement of MHC class II associated invariant chain (Ii) in antigen processing and presentation in different dendritic cell (DC) populations.
DC is recognized as the most potent antigen presenting cells with the unique ability to initiate and maintain primary immune responses. Using Ii knockout mice with MHC II/GFP knock-in (MHC II/GFP Ii-/-) as well as imaging techniques like fluorescence recovery after photobleaching (FRAP), the concise trafficking of distinct molecules will be visualized in live cells in dependence of various Ii mutants. Moreover, functional consequences of these Ii mutants on the T cell stimulatory capacity will be determined. By gene profiling, differences between mature DC populations using distinct pathogenic stimuli will be analysed, with special emphasis on the effects on their T cell stimulatory ability.
Furthermore, the function of the Ii splice variant p41 will be determined. Only by precisely knowing the possible targets of pathogenic and tumorigenic interference will it be possible to improve existing and develop new clinical approaches using DC.
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