Research Interests.
Major Histocompatibility Complex (MHC) class I molecules play a fundamental role in orchestrating the immune system and inducing protective immune responses against tumours and pathogens. They do this by presenting peptides derived from pathogen and tumour proteins to the immune system. Our labs explore the pathway that controls peptide selection onto MHC-I molecules. This has important translational potential given the importance of MHC molecules in infectious disease, cancer, and autoimmunity.
Boyle lab
In 2013, the Boyle lab discovered a completely novel MHC-I specific component in the antigen processing and presentation pathway, a protein called TAPBPR. Our research is focused on characterising the function of TAPBPR on human MHC-I molecules. We discovered that TAPBPR is an MHC-I peptide editor that shapes the final antigen repertoire displayed for immune recognition. We revealed an editing loop region of TAPBPR (consisting of residues K22-D35) is involved in mediating peptide dissociation of MHC-I, thus revealing new mechanistic insight into how peptides are selected for immune recognition. Furthermore, we found that by serving as a molecular bridge between peptide-receptive MHC-I and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), TAPBPR promotes the glucosylation of the glycan attached on MHC-I, subsequently causing the MHC-I to recycle back to the peptide loading complex.
Although TAPBPR normally functions as an intracellular peptide editor, we discovered that recombinant TAPBPR can be used to promote peptide exchange directly on plasma membrane expressed MHC-I. Thus, recombinant TAPBPR can be utilised to decorate cells with immunogenic peptides. This ability to make cells recognisable by the immune system opens up the potential to utilise the function of TAPBPR therapeutically. This might serve as a valuable resource in the fight against cancer.
The Ins and Outs of TAPBPR.
Ilca TF & Boyle LH. 2020.
Altenburg lab
To evade immune detection, viruses have evolved strategies to manipulate MHC-I molecules directly or to interfere with other proteins in the antigen processing and pathway. The Altenburg lab explores the MHC-I pathway in virus infections to i) gain a better understanding of immune detection of virus-infected cells and ii) to explore novel strategies by which viruses evade MHC-I pathway proteins. Ultimately, the characterisation of these dynamics can inform the development of novel vaccines and therapeutics.