Mayo Clinic researchers announced on Apr. 6 the development of a new method to identify which proteins are most likely to trigger an immune response, a finding that could influence transplant care and regenerative medicine. The results, published in Biomaterials, suggest that not all proteins provoke immune reactions equally.
This research is important because understanding which proteins cause harmful immune responses can help improve outcomes in organ transplantation, tissue engineering, and related fields. It challenges previous assumptions by ranking proteins based on both their abundance and their ability to activate the immune system.
The team introduced the Ratio of Immunogenicity (ROI), a measurement combining how much of each protein is present with its strength in activating immunity. By applying ROI across hundreds of proteins, they found patterns not previously recognized. Notably, mitochondrial proteins stood out as more likely to evoke strong immune responses than those from other cell parts—making up over a quarter of the most immunogenic group identified. Mitochondria's evolutionary history as descendants of ancient bacteria may explain this heightened sensitivity.
"We think the body has never fully accepted mitochondria as part of itself - they're normally hidden inside the cell, and when they're exposed, the immune system may still recognize them as foreign," said Dr. Griffiths.
Researchers say this approach could also help pinpoint key targets for rejection in organ transplants or guide therapies for infectious diseases and cancer biology. In transplantation specifically, identifying highly immunogenic proteins might allow for better biomarkers or more targeted treatments.
Dr. Griffiths' laboratory is using these findings to refine engineered tissues for clinical use by removing problematic proteins while maintaining structural integrity needed for healing. "This study fills a critical gap in knowledge," Dr. Griffiths said. "If we want to build regenerative therapies and implants that are truly safe and effective, we need to understand not just that the immune system is reacting, but what exactly it is reacting to. That understanding is what will help move better products to patients."
