New research uncovers hidden rules of immune response, opening doors for better vaccines and immunotherapies

SEATTLE – Scientists at the Institute for Systems Biology (ISB) have uncovered key insights into how T cells – the body's frontline immune soldiers – respond to infections like COVID-19. Their research suggests that the disease fighting functions of T cells are strongly influenced by the genetic sequence of the T cell receptors and the genetic sequence of the pathogen targets that trigger T cell activation. While variations in immune responses indicate some unpredictability, this discovery enhances our understanding of immune cell behavior, offering new possibilities for improving treatments and vaccine strategies.  

To make this breakthrough, ISB researchers developed APMAT, a powerful tool that integrates computational analysis with lab experiments to process large datasets and detect patterns in T-cell behavior. By analyzing COVID-19 patients, researchers developed insights for predicting how specific T cells would respond to specific viral targets, including predicting which T cells would evolve over time or provide long-term immunity, and which ones would disappear as the infection resolves.

“For decades, scientists have debated whether immune responses are random or follow set rules,” said Dr. Jingyi Xie, lead author of the study. “Our findings show that T cells follow a predictable pattern based on their genetically encoded molecular interactions.”

These findings could help scientists refine immune response strategies to improve long-term protection against diseases. Furthermore, these insights could contribute to more precise treatments for cancer and autoimmune diseases.

“If we can predict how a T cell will behave, we can create better treatments that train the immune system to work more effectively,” said ISB President and Professor Dr. Jim Heath, senior author of the study. “This research provides valuable insights into how immune responses can be better engineered for disease prevention and treatment.”

The ISB team plans to expand their research to see if these patterns apply to other diseases and different populations. Their goal is to apply these insights toward more personalized and effective immune-based therapies.

"Understanding the fundamental rules of T cell activation could be a game-changer for immunology," Heath said.

The study was published in Nature Communications and is available here. 

About ISB

Institute for Systems Biology (ISB) is a collaborative and cross-disciplinary non-profit biomedical research organization based in Seattle. We focus on some of the most pressing issues in human health, including aging, brain health, cancer, chronic illness, infectious disease, and more. Our science is translational, and we champion sound scientific research that results in real-world clinical impacts. ISB is an affiliate of Providence, one of the largest not-for-profit healthcare systems in the United States. Follow us online at isbscience.org, and on YouTube, Facebook, LinkedIn, X, Bluesky, and Instagram.