28 Aug 2024
“It takes two to tango” - Fundamental research uncovers the molecular dance for activating gamma-delta cells
Melbourne researchers have solved a decades-long mystery by elucidating the intricate mechanisms that govern how gamma-delta T cells, a crucial component of the immune system, recognise and respond to infected or cancerous cells.
In a study co-led by Dr Adam Uldrich, Senior Research Officer, and Professor Dale Godfrey, Laboratory Head, both at the Doherty Institute, researchers discovered that gamma-delta T cells require not one, but two specific signals from infected or cancerous cells to activate.
The University of Melbourne’s Dr Thomas Fulford, Research Assistant at the Doherty Institute, lead author of the study published in Nature Immunology, explained that the research provides a clearer understanding of gamma-delta T cells’ role in immune responses.
“We discovered that it’s actually two proteins from the ‘butyrophilin’ family that drive gamma-delta T cell immune responses in humans,” said Dr Fulford.
“Our research revealed the molecular process by which gamma-delta T cells detect butyrophilins and showed that these two proteins must undergo a structural change to be recognised by the immune cells.
“This is the first time ever that the molecular structure of T cell receptor interacting with a butyrophilin protein has been described.”
Dr Uldrich said these groundbreaking findings deepen our understanding of immune system activation, crucial for developing future therapies.
“While our discovery is still in its early stages, it lays a solid foundation for future studies. We hope these insights will one day lead to techniques for manipulating these cells to enhance protection against various diseases,” said Dr Uldrich.
Professor Godfrey emphasised the potential impact of this research.
“Understanding this dual recognition mechanism opens up new possibilities for immunotherapy. It could lead to innovative treatments for cancer and infectious diseases, ultimately improving patient outcomes.”
This detailed examination of how gamma-delta T cells are activated by specific signals reveals the intricate dynamics of immune responses, potentially leading to significant improvements in health outcomes for patients with infectious diseases and cancer.
- Peer review: Fulford T, Soliman C, Castle R et al. Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers. Nature Immunology (2024). https://doi.org/10.1038/s41590-024-01892-z
- Funding: Funding support was provided by the Miller Foundation Research Accelerator fund, the Cancer Council of Victoria, the National Health and Medical Research Council of Australia (NHMRC), the Australian Research Council (ARC), Cancer Council Victoria and the Victorian Department of Health and Human Services.
- Collaboration: CSIRO, Olivia Newton John Cancer Research Institute, CSL Limited.