New insights into our immune responses could pave the way for innovative treatments and vaccines.
Research by Pirbright scientists, as part of an international collaboration, has informed a new paper published in the Journal of Biological Chemistry. The study shows an important section of our immune system involving the molecule MR1 and MAIT cells is evolutionarily conserved in multiple species.
By functioning as a molecular 'alarm system,' MR1 can present molecules from a diverse range of bacteria and fungi, alerting the immune system, specifically MAIT cells, of infectious bacteria or fungi or to monitor our microbiome.
This mechanism is supported across species, enabling comparative studies. Findings from this study could 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.
Former Pirbright researcher Dr Matthew Edmans, lead author and Postdoctoral Scientist from Professor Paul Klenerman’s group in the Experimental Medicine Division at NDM 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.’
Oxford University collaborated with The Doherty Institute, The Pirbright Institute, The Roslin Institute, Utrecht University (NL) and The University of Queensland (AUS) to assess the conservation of the MR1/MAIT cell interaction across species. They tested MR1 multimers from multiple species to identify MAIT cells in distantly related species, including humans, cows, mice, sheep and pigs.
Dr Eckle, a senior author of the study, was previously part of the team that originally developed MR1 multimers in various species. For this study, her group developed and tested new MR1 multimers specific to cows and pigs. The MR1 multimers successfully identified MAIT cells in most animals, revealing a high level of conservation of this immune mechanism.
Key findings include:
- Humans possess the largest population of MAIT cells, with a tenfold greater proportion than other species.
- Mice have approximately 100-fold fewer MAIT cells compared to humans.
- Pigs showed no obvious population of MAIT cells, despite encoding 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 as well as 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 novel therapies.
The study was published in the Journal of Biological Chemistry, read the full research paper.