Lipid antigens and CD1-reactive T cell discovery

Most T-cells hunt fragments of proteins, but a hidden army of immune cells responds to fats instead—and these lipid-reactive T-cells are abundant in human tissues and linked to disease. This matters because nearly all T-cell research has focused on protein targets, leaving a blind spot in our understanding of immunity. The molecules that present lipids to T-cells, called CD1 proteins, are virtually identical across the human population, meaning any rules discovered here could apply to everyone. The team combines lipid chemistry, structural biology, and a novel lipidomic platform to figure out how lipid antigens are presented to T-cells in health and disease. If successful, this fundamental science will provide the first open tools for predicting CD1 antigens and identifying the T-cell receptors that recognise them. It will also uncover agonist and antagonist lipids that could be developed into therapies. This is primarily curiosity-driven research into a poorly understood branch of the immune system—but similar fundamental work on protein-reactive T-cells has already led to cancer immunotherapies and vaccines. A deeper grasp of lipid-reactive T-cells could open an entirely new axis for treating autoimmune diseases, infections, and metabolic disorders.