Researchers have created a ‘lipid map’ that provides insights into immunology
“Splash Down.” The image provides a perspective for thinking about how tryptic antigens are recognized in aqueous solution. Four lipid-presenting molecules, CD1a, CD1b, CD1c and CD1d, including the trimeric CD1 lipid complex, project to the surface of the blue and aqueous environment surrounding the T cell. Image credit: Dr. Erica Tandoori.
An international team of scientists has developed a method for the simultaneous detection of thousands of lipid molecules that are presented to T cells in the human immune system.
The study, co-led by Professor Dr. Branch Modi, MD, of the Department of Rheumatology, Immunology and Inflammation at Brigham and Women’s Hospital, and Adam Sahin, PhD, of the Monash Biomedical Discovery Institute, a collaboration between researchers from Oxford, UK, Monash University in Melbourne, Australia, and Groningen, Netherlands. . The results were published today in cell.
The team has developed a new, sensitive method to detect more than 2,000 lipids bound to CD1 antigen-presenting molecules, which expose antigens to the human immune system.
While scientists have long known that T cells recognize antigens, until the 1990s, these antigens were always thought to be peptides derived from proteins. Because lipids are not encoded by genes, but rather are synthesized by enzymes and formed in membranes, they have completely different functions and locations in the cell.
The ability to measure multiple lipid antigens simultaneously will allow future researchers to screen for any disease-related lipids with the list of candidate lipid antigens from this map and potentially make disease connections.
Their efforts resulted in the first integrated lipid map of CD1, which could help guide the research and discovery of lipid blockers and T-cell antigens and support the view that lipids normally influence immune responses.
The research builds on previous methods for separating cellular lipids in a single chromatographic system, which provides only a limited perspective. The new structural biology work, conducted by Dr. Sahin, an ARC DECRA Fellow, has shown how lipids fit into proteins using size-dependent mechanisms.
Taken together, the structures and biochemistry detail the rules regarding the size, shape, and chemical content of the types of lipids that can bind CD1 and trigger a T-cell response, either activation or deactivation. It’s the latest in a series of studies dating back to the 1990s, when Brigham scientists discovered that T cells could recognize lipid antigens.
“In this ambitious decade-long multidisciplinary study, we have described the full spectrum of cellular lipids that can be presented to T cells. Furthermore, we have combined 25 years of structural biology data, as well as new data collected at the Australian Synchrotron ANSTO, to standardize the rules governing molecular mechanisms in lipid presentation. “Our hope is that the data generated in this study will serve as a basis for future research in the field of lipid immunity.”
“The Brigham Hospital provides an environment where clinicians and scientists from different fields can collaborate,” Professor Moody said. “This multidisciplinary effort has included biophysical techniques related to mass spectrometry and biological techniques related to lipid chemistry. Lipids have reported immunological outputs, and a method for identifying lipids has been developed.” Proven by X-ray crystallography.”
Read the full post at celltitled CD1 lipids reveal lipid binding motifs and size-based antigen presentation mechanisms
doi: 10.1016/j.cell.2023.08.022.
About the Monash Biomedical Discovery Institute
Committed to making discoveries that will reduce the future burden of disease, the newly established Monash Biomedical Discovery Institute at Monash University brings together more than 120 world-renowned research teams. Spanning seven discovery programs across cancer, cardiovascular disease, development, stem cells, infection, immunology, metabolism, diabetes, obesity and neuroscience, Monash BDI is one of Australia’s largest biomedical research institutes. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to improve lives through discovery.
