JBC: The "Close Button" of the Immune System

Scientists have discovered what shuts down the molecular alarm system, which plays a vital role
in our immune response.

MR1 (MHC Class I-related molecule) is an antimicrobial superhero – a protein that exists in every cell of the human body and acts as a molecular alarm system when a bacterial infection or cancer appears, alerting
powerful cells in the immune system, white blood cells.

While previous groundbreaking studies have revealed the cellular mechanisms on which MR1 activation depends, so far little
has been known about how the alerts for MR1 are "turned off.

The study, published in the Journal of Cell Biology and co-led by Dr Hamish McWilliam of the University of Melbourne and Professor Jose Villadangos of the Doherty Institute and Bio21 Institute, reveals key molecular mechanisms
that control MR1 expression.

Dr.

"Once in the body, MR1 can no longer signal to white blood cells, which effectively shuts down the immune response
.

In their experiments, the team found that by removing AP2, or mutation MR1 from cells, they could regulate the activation of MR1, which in turn stimulates or inhibits the presence of
white blood cells.

Dr.

"By understanding how to turn off MR1, we may be able to block or enhance the immune response, using it to control immunity to pathogens or tumors," said
Dr.

The study is the result of collaboration between the Doherty Institute, the University of Melbourne, Monash University, the University of New South Wales, the University of Queensland, Victoria University of
Wellington (New Zealand), the Walter and Eliza Hall Medical Institute and Université de Nantes (France).

essay

A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells