Groundbreaking Research Exposes Immune System’s “Off Button”

Scientists have found what turns off the molecular alarm system, which is crucial in our immune response.

Scientists have discovered what turns off the molecular alarm system that plays a critical role in our immune response.

The antibacterial superhero MR1 (MHC class I-related molecule) is a protein found in every cell of the human body that functions as a molecular alarm system, alerting powerful cells of our immune system, our white blood cells, when cancer or bacterial infection is present.

While prior groundbreaking research revealed the cellular machinery that MR1 depends on to activate, nothing was understood about how the MR1 alarm is “turned off” until now.

The research, co-led by Dr. Hamish McWilliam of the University of Melbourne and Professor Jose Villadangos of the Doherty Institute and the Bio21 Institute, was published in the Journal of Cell Biology and shows the essential molecular mechanism that controls MR1 expression.

“What we found is that there are proteins – called AP2 (adaptor protein 2) – inside our cells that bind to MR1, and drag it inside the cells,” Dr. McWilliam explains.

“Once inside, MR1 can no longer signal to white blood cells anymore, which effectively turns off the immune response.”

In their experiments, the research team found that by deleting AP2 in cells or mutating MR1, they could regulate MR1’s activation which in turn stimulates or inhibits the presence of white blood cells.

Dr. McWilliam says this is an exciting discovery as it unlocks a fundamental understanding of the biology of MR1 and contributes to global efforts to design immune-boosting treatments.

“By understanding how to turn off MR1, we might be able to block or increase immune response, to harness it and control immunity to pathogens or tumors,” Dr. McWilliam says.

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