Breakthrough study uncovers cause of human immune system shutdown

Breakthrough study uncovers cause of human immune system shutdown

Scientists have discovered what causes the molecular alarm system to be turned off, a key element in the human immune response, which could lead to the development of treatments with enhanced immunity.

The antimicrobial supermolecule MR1, the class I MHC-related molecule (MCH – a group of genes that encode proteins on the surface of cells that help the immune system recognize foreign substances) is a protein found in every cell of the human body, which functions as a molecular alarm system, alerting the powerful cells of the human immune system, the white blood cells, to the presence of cancer or bacterial infection.

Although earlier groundbreaking studies have clarified the cellular machinery on which MR1 depends for activation, there has been no clear understanding of how the alarm molecule MR1 is “turned off”.

A study by scientists led by Dr Hamish McWilliam of the University of Melbourne and Professor Jose Villadangos of the Doherty Institute and Bio2 Institute, Australia, and published in the Journal of Cell Biology, has clarified the molecular mechanism required. weakly controls the expression of MR1.

The human immune system senses the bacteria when cells armed with a protein called ’MR1’ capture small molecules (antigens) and give the cells a powerful immune system called ” MAIT cells”. Photo: Peter Doherty Institute for Infection and Immunity.

Dr McWilliam explains: “What the team found is that there are proteins, called AP2 (conjugation protein 2) inside human cells that bind to MR1 and pull the MR1 molecule inside the cell. cell. Once inside, MR1 can no longer signal the white blood cells, which may have effectively shut down the immune response.”

In their experiments, the team found that, by deleting AP2 in cells or mutating MR1, the scientists could modulate the activation of MR1, thereby stimulating or inhibiting the expression of MR1 cells. presence of white blood cells.

Dr McWilliam commented, “This is an exciting discovery as it opens up a fundamental understanding of the biology of MR1 and contributes to the global effort to design and develop immune-boosting treatments.

“By understanding how MR1 is turned on and off, we can suppress or increase the immune response, manipulating and controlling human immunity to pathogens or tumors,” said Dr McWilliam. 

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