26 Jun 2024
Conserved immune system interactions across species could transform microbial infection control
An international team of researchers has discovered that an important part of the immune system, involving MR1 (a molecule that helps detect infections) and MAIT cells (immune cells that respond to these infections) is similar across different species.
MR1 acts as a molecular 'alarm system' by detecting and presenting molecules from a diverse range of bacteria and fungi to alert MAIT cells, which then respond to infections or monitor our microbiome.
The research collaborators found that the fundamental mechanism of how MR1 interacts with MAIT cells is similar across different species, suggesting that this interaction, shared across species, is important for the function of the immune system and has remained relatively unchanged through evolutionary time.
Findings from this study published in the Journal of Biological Chemistry, could enable comparative studies and inform new strategies for combating a wide range of microbial infections, by comparing similarities and differences in immune responses among human and animal samples. This new research could pave the way for innovative treatments and vaccines.
Dr Matthew Edmans, first author and Postdoctoral Scientist in the Nuffield Department of Medicine at Oxford University said, “Understanding the cross-species functionality of MAIT cells can inform how we develop therapies for infectious diseases in humans and animals. Our findings open new avenues for biomedical research and therapeutic development.”
The researchers examined the conservation of the MR1/MAIT cell interaction across species. They tested MR1 multimers, laboratory-engineered molecules made of multiple MR1 to swiftly and accurately find MAIT cells, from multiple species to identify MAIT cells in distantly related species, including humans, cows, mice, sheep and pigs.
Together with her team, University of Melbourne’s Dr Sidonia Eckle, a senior author of the study and Group Leader at the Doherty Institute, developed and tested new MR1 multimers specific to cows and pigs.
“The MR1 multimers of each species successfully identified MAIT cells in most animals, showing the MAIT-MR1 immune axis is highly conserved,” said Dr Eckle.
Key findings include:
- Humans have the most MAIT cells, ten times more than other species.
- Mice have about 100 times fewer MAIT cells compared to humans.
- Pigs lack a noticeable population of MAIT cells despite having the MR1 protein.
Dr Edmans said, “The remarkable conservation of the MAIT-MR1 axis underscores its immunological importance. However, the variation in MAIT cell numbers among species suggests potential redundancy or compensation by other immune cells.”
The study’s findings prompt further research into the role of MAIT cells across different species and future studies will focus on understanding why some species have fewer or no MAIT cells and exploring alternative immune mechanisms. The validated MR1 multimers will be instrumental in these investigations, advancing our knowledge of immune responses and informing the development of new therapies.
Peer review: Edmans M, et al. MAIT cell-MR1 reactivity is highly conserved across multiple divergent species. Journal of Biological Chemistry (2024). https://doi.org/10.1016/j.jbc.2024.107338
Funding: University of Oxford, National Health and Medical Research Council (NHMRC), The University of Melbourne, Australian Research Council (ARC), National Institutes of Health (NIH), Wellcome Trust, The Pirbright Institute, The Roslin Institute.
Collaboration: The study is the result of a collaboration between Oxford University, the Doherty Institute, the Pirbright Institute, the Roslin Institute, Utrecht University and The University of Queensland.