Structural breakthrough sheds light on unique immune cells
T cells are a powerful immune cell that serve as sentinels of the immune system, patrolling the body for signs of infection or disease. Yet, how T cells recognise these markers through their T cell receptor (TCR) to remove pathogens is unclear.
Researchers from Monash University’s Biomedicine Discovery Institute (BDI) have uncovered how a poorly understood immune cell detects and responds to markers of infection and cancer. Published today in Nature Communications, a research team from Monash University has identified how a unique immune cell, known as a ℽ𝛿 (gamma delta) T cell, recognises pathogens to potentially ward off disease.
During times of cellular stress such as bacterial infection, cells can present molecules on their cell surface for recognition by the immune system. One of these molecules, CD1d, can present a class of small molecules known as lipid antigens. Although CD1d was known to activate ℽ𝛿 T cells, how the ℽ𝛿 TCR recognised CD1d remained elusive.
First-author Dr Michael Rice, a Faculty of Medicine Research Fellow, said “ ℽ𝛿 T cells are increasingly realised as an important immune cell. However, our understanding of their importance had previously been hampered by a lack of knowledge of how they recognise pathogens.”
The research team identified how the ℽ𝛿 T cell receptor recognised CD1d. Utilising the Australian Synchrotron, the researchers were able to determine the protein structure of a ℽ𝛿 TCR recognising CD1d.
This structure illuminated that ℽ𝛿 T cells recognise CD1d in a manner that is unique compared to other T cells. This provided precise molecular information on how ℽ𝛿 T cells sense markers of disease. Combined with biochemical, functional and high-resolution microscopy-based techniques, the team identified how ℽ𝛿 T cells recognised and responded to CD1d, a marker of bacterial infection.
According to Dr Rice: “By investigating a known ℽ𝛿 T cell antigen we were able to tease apart the key drivers of ℽ𝛿 T cell activation. This provides a strong foundation for further characterisation of ℽ𝛿 T cells that are an emerging therapeutic target.”
This research project was supported by funding from the National Health and Medical Research Council (NHMRC) and the Australian Institute of Nuclear Science and Engineering.
Read the full paper published in Nature Communications, titled “ℽ𝛿 T cell receptor recognition of CD1d in a lipid-independent manner”.
