Ground-breaking research uncovers the immune system’s ‘Off Button’

Illustration of Human Immune System
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Description of the Human Immune System

The immune system protects your body from external influences.

Scientists have discovered what turns off the molecular alarm system so important 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 acts as a molecular alarm system that alerts the powerful cells of our immune system, the white blood cells, in the event of cancer or bacterial infection. present

Although previous groundbreaking studies have revealed the cellular mechanisms upon which MR1 activation depends, until now nothing was understood about how MR1 signaling is “turned off”.

Dr. who led the research. Hamish McWilliam of the University of Melbourne and Professor Jose Villadangos of the Doherty Institute and the Bio21 Institute published in the journal. Journal of Cell Biology and indicates the underlying molecular mechanism controlling MR1 expression.

Immune System Bacteria

Our immune system senses bacteria when cells equipped with a protein called ‘MR1’ capture small molecules (antigens) and present them to powerful immune cells called ‘MAIT cells’. Credit: Peter Doherty Institute of Infection and Immunity

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

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

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

Dr. McWilliam says this is an exciting discovery that opens up a fundamental understanding of MR1’s biology and contributions to global efforts to design immune-enhancing therapies.

Dr. McWilliam says.

Reference: “A specialized tyrosine-based endocytosis signal in MR1 directs antigen presentation to MAIT cells” by Hui Jing Lim, Jacinta M. Wubben, Cristian Pinero Garcia, Sebastian Cruz-Gomez, Jieru Deng, Jeffrey YW Mak, Abderrahman Hachani, Regan J Anderson , Gavin F. Painter, Jesse Goyette, Shanika L. Amarasinghe, Matthew E. Ritchie, Antoine Roquilly, David P. Fairlie, Katharina Gaus, Jamie Rossjohn, Jose A. Villadangos, and Hamish EG McWilliam, 21 September 2022 Journal of Cell Biology.
DOI: 10.1083/jcb.202110125

The research was funded by the National Health and Medical Research Council, the Australian Research Council, the Australian Research Council Center of Excellence for Advanced Molecular Imaging, the National Institutes of Health, the New Zealand Ministry of Business Innovation and Employment and Horizon 2020. Framework Program.

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