Autophagy: a multifaceted pathway in immunity

© 2014 Natalie Louise PattersonAutophagy is an evolutionary conserved pathway of protein degradation. In recent years, autophagy has been shown to play numerous critical roles in the immune system, contributing to both immune cell homeostasis and survival, and the initiation of adaptive immune responses through the putative delivery of antigen to MHCI and MHCII antigen presentation pathways. The objective of this thesis was to further elucidate autophagy in both T cell maintenance and survival and in MHCII antigen presentation and MHCI antigen cross-presentation. To begin to assess autophagy in T cells, it was demonstrated that both naïve and in vitro activated T cells utilised the autophagy pathway. In addition, it was shown that atg5 was essential for an intact naïve T cell compartment and efficient T cell proliferation in vitro. As T cells switch metabolism profiles to meet changing energetic demands, it was hypothesised that T cells regulate autophagy in response to these cues. To monitor autophagy regulation within T cells, the GFP-LC3 mouse model was utilised. However, the GFP-LC3 mouse model was proven to be inappropriate for the study of autophagy regulation due to differential expression patterns of endogenous LC3B and transgenic GFP-LC3 in activated T cells. To extend upon findings that autophagy was involved in MHCII antigen presentation and potentially in MHCI antigen cross-presentation, antigen presentation assays were performed in the presence of the autophagy inhibitor 3-MA. It was demonstrated that 3-MA inhibition resulted in reduced MHCII antigen presentation and MHCI antigen cross-presentation of exogenous antigen. It was hypothesised that the CD11cCre x Atg7F/F mouse model could be employed to further investigate autophagy in antigen presentation. However, at the conclusion of this study, the CD11cCre x Atg7F/F mouse model was undergoing optimisation