The body immune system safeguards your body from external intruders.
Researchers have found what shuts off the molecular alarm system, which is vital in our immune response.
Scientists have discovered what turns off the molecular alarm system that plays a crucial function in our immune response.
The anti-bacterial superhero MR1 (MHC class I-related particle) is a protein found in every cell of the human body that functions as a molecular alarm system, informing effective cells of our immune system, our white blood cells, when cancer or bacterial infection exists.
While prior cutting-edge research revealed the cellular equipment that MR1 depends upon to activate, nothing was comprehended about how the MR1 alarm is “shut off” previously.
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 necessary molecular mechanism that manages MR1 expression.
Our immune system senses bacteria when cells geared up with the protein called MR1 captures little particles (antigens) and present them to powerful immune cells called “MAIT cells”. Credit: The Peter Doherty Institute for Infection and Immunity
” What we discovered 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 describes.
” Once inside, MR1 can no longer signify to leukocyte any longer, which effectively switches off the immune reaction.”
In their experiments, the research study team found that by deleting AP2 in cells or mutating MR1, they could control MR1s activation which in turn hinders the presence or stimulates of white blood cells.
Dr. McWilliam states this is an exciting discovery as it opens a basic understanding of the biology of MR1 and contributes to international efforts to design immune-boosting treatments.
” By understanding how to shut off MR1, we might be able to block or increase immune reaction, to harness it and manage immunity to tumors or pathogens,” Dr. McWilliam says.
Referral: “A specialized tyrosine-based endocytosis signal in MR1 controls antigen discussion to MAIT cells” by Hui Jing Lim, Jacinta M. Wubben, Cristian Pinero Garcia, Sebastian Cruz-Gomez, Jieru Deng, Jeffrey Y.W. 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 E.G. McWilliam, 21 September 2022, Journal of Cell Biology.DOI: 10.1083/ jcb.202110125.
The research study was funded by the National Health and Medical Research Council, the Australian Research Council, the Australian Research Council Centre of Excellence in Advanced Molecular Imaging, the National Institutes of Health, the New Zealand Ministry of Business Innovation and Employment, and the Horizon 2020 Framework Programme..