For decades, human alpha beta T cells were thought to solely or predominantly recognize peptide antigens bound to MHC proteins. However CD1 proteins bind diverse lipid antigens and display them to T cells. These recent studies provide a new perspective on T cell function that expands the range of natural antigens for T cells to include many types of cellular lipids. CD1 proteins are expressed on key antigen presenting cells including B cells, myeloid dendritic cells and Langerhans cells. Many studies now show that CD1 proteins bind and display bacterial antigens for T cell recognition. However, information on lipid autoantigens has been very limited. Using new strategies by which autoantigens are extracted from human tissues and then added back to CD1a proteins, we report that lipid autoantigens for CD1a are hydrophobic oils including squalene, wax esters and free fatty acids. In human patients, CD1a autoreactive T cells are common in the blood and home to skin, joints and other tissues. Certain CD1a autoreactive T cells produce high levels of interleukin-22, a specialized cytokine implicated in inflammation and wound repair, whose production is associated with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) activity. Whereas clinicians have long understood that oils and lipids have unexplained immunological properties, these studies provide a specific cellular mechanism of T cell response to lipids. Further, these studies of human polyclonal T cells suggest a new mechanism by which tissue damage releases lipid autoantigens and promote cytokine-driven inflammation in the joints and skin. Because all human express nearly identical CD1a proteins, these lipids can be developed as T cell immunomodulatory agents for use in all patients, regardless of the MHC background.
Disclosure of Interest None declared