Breakthrough study discovers the immune system's "off button"

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

Antimicrobial superhero MR1 (MHC class i related molecule) is a protein present in every cell of the human body that functions as a molecular alert system to alert powerful cells, white blood cells, in the immune system when cancer or bacterial infection arises
.

While previous groundbreaking studies have revealed the cellular mechanisms on which MR1 activation depends, until now, no one knew
how MR1 alerts were "turned off.
"

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

When cells containing the MR1 protein capture small molecules (antigens) and submit them to MAIT cells, a powerful immune cell, our immune system is able to sense bacteria
.
fig

"We found that there is a protein in our cells called AP2 (adapter protein 2) that binds to MR1 and drags it inside the cell," explains Dr
.
McWilliam.
"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 the mutation MR1 from cells, they could regulate the activation of MR1, thereby stimulating or inhibiting the presence of
white blood cells.

Dr.
McWilliam said this is an exciting discovery because it opens up a fundamental understanding of the biology of MR1 and contributes to global efforts to
design immunoenhancing therapies.
"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.
"

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