Going places: Intracellular trafficking for effective immunity
Autophagy and antigen presentation
Autophagy is a pathway that cells use to eat intracellular material. Autophagy is implicated in pathways of antigen presentation and immunity.
We have identified that CD8+ dendritic cells, which are specialised in cross-presentation, exhibit enhanced autophagy. We have in vivo models in which critical autophagy genes are lacking in specific immune cell types, including primary dendritic cells.
We are evaluating the contribution of autophagy to antigen presentation and immune outcomes in models of infection, autoimmunity and tumours. With our collaborators, we are also investigating the role of autophagy in primary human dendritic cells.
Figure 1: Autophagosomes in cross-presenting dendritic cells.
Figure 2: Amnis image flow cytometry of autophagosomes in dendritic cells.
Ubiquitinylation of surface immunoreceptors
Ubiquitin plays an important role in the surface expression of immunoreceptors. It acts as a molecular switch that can tag surface molecules for internalisation and degradation in lysosomes.
We are investigating the control by ubiquitination of cell surface expression of different immune molecules including MHCII and CD86 (Figure 3). We have in vivo models in which these molecules are no longer ubiquitinated. Using proteomics and CRISPR-cas9 technology, we are defining molecules involved in the ubiquination of surface immunoreceptors in different primary immune cells.
Figure 3: Example of ubiquitination associated with MHCII in dendritic cells.
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