Study improves understanding of how immune cells communicate

The discovery of a new protein, UBL3, could play an important role in the development of more efficient vaccines and better immunotherapies.

The discovery of a new protein, UBL3, could play an important role in the development of more efficient vaccines and better immunotherapies.

New factors that regulate key immune receptors have been uncovered, thanks to a research collaboration between the Department of Biochemistry and Pharmacology at Bio21 Institute of Molecular Science and Biotechnology, Walter and Eliza Hall Institute and Peter Doherty Institute for Infection and Immunity.

Research published in Nature Communication explained how cells alert each other via receptors on the cell surface during an immune response to infection or vaccines.

Two of these key immune receptors, MHC II and CD86, are “tagged” for degradation with another small molecule called ubiquitin, which is a signal to reduce their presence on the cell surface. These changes in cell surface receptors affects how immune cells communicate.

The study discovered a new protein, UBL3, that’s required for ubiquitin “tagging” of MHC II and CD86.

Lead author Associate Professor Justine Mintern of the Department of Biochemistry and Pharmacology, explained: “This is the first time UBL3 is implicated in immunity. Now we know if this process is disrupted, some immune responses are dysfunctional.”

Understanding the regulation of key immune receptors is important in the development of more efficient vaccines and better immunotherapies.

Haiyin Liu, a research fellow in immune receptor trafficking who is a postdoctoral researcher in the Justine Mintern laboratory, added: “Deepening our understanding of immune regulation will help address the global challenges of improving vaccines and immunotherapies.”

The work came about because researchers were curious if MARCH1 – which performs the tagging of MHC II and CD86 – requires any co-factors to do its work and screened the mouse genome for genes affecting MHC II.

“We were intrigued to see UBL3 pop up, which is actually very similar to the “tag” ubiquitin itself. Not much was known about it, so we started investigating,” Haiyin said.

Next, the study team is curious to understand if the mechanism of UBL3-mediated receptor “tagging” also extends to other receptors – or even viral proteins.

“MARCH1 and MARCH8 can target HIV envelope proteins and the SARS-CoV2 spike protein – so, we want to find out if UBL3 is involved here. We also want to learn how exactly it functions on a molecular level,” A/Prof Mintern added.

Find out more about the research underway by the Department of Biochemistry and Pharmacology.