Cross-presentation of exogenous ROP proteins by antigen presenting cells to MHC class I and class II pathways
Nicola Burgess-Brown (external)
Immunotherapy including therapeutic vaccines provides great hope for cancer treatment. Understanding the mechanisms of antigen presentation is helpful for optimal design of an immunotherapy. Exogenous protein antigens are usually cross-presented mainly to MHC class II pathway and stimulate strong CD4 T cells and antibody responses, while endogenous antigens (viral protein produced inside cells) stimulate CD8 T cells. In our previous in vivo and in vitro studies, we have found that recombinant overlapping peptides (ROP), a protein form of (exogenous) antigens, stimulate both CD4 and CD8 T cells. The mechanism behind the phenotype is not clear. In this project, we will utilize available ROP antigens (ROP-HPV, ROP-survivin, ROP-TB and ROP-OVA) to investigate antigen presentation of ROP in a cellular model, including primary DCs and DC2.4 (a dendritic cell line). We will observe the endocytosis/phagocytosis of ROPs and study how ROPs will be presented and what fragments (peptides) are presented on the surface of the antigen presenting cells. The knowledge learned from this study will be very helpful for future ROP vaccine/diagnostic design and development.
We will collaborate with Dr Nicola Burgess-Brown of the Structural Genomics Consortium (SGC) and take advantage of the knowledge and the core facilities at both the Department of Oncology and SGC for this study. In addition to understand the in-depth knowledge of immunology (especially the antigen presentation), the student will learn the following technologies (core facilities): tissue culture (Oncology), protein expression and purification (SGC), DC purification and culture, confocal microscopy (Oncology), flow cytometry (Oncology) and mass spectrometry (SGC). The project will be sponsored by the Oxford University spinout company Oxford Vacmedix UK Ltd. There will be opportunities to collaborate with OVM and its associated companies in South Korea who are very specialised in translational dendritic cell technology.