Dr Stephen Daley leads the Developmental Immunology Research Group.
We try to understand the cause of autoimmune disease. The immune system has the potential to cause autoimmune disease in everyone. Although it may seem effortless, staying free of autoimmune disease requires constant peacekeeping between the immune system and the rest of the body. This peacekeeping is called immune tolerance.
T cells are important for fighting infections and cancers, but not all T cells are “fighters”. Some T cells are peacekeepers, such as T-regulatory cells. To maintain immune tolerance, T-regulatory cells must “see” a by-product of healthy tissue called a self-antigen. Our research focusses on how T-regulatory cells develop in the thymus. We are testing the idea that autoimmune disease arises in people who lack a self-antigen that T-regulatory cells can “see”.
If autoimmune disease arises from the absence of a self-antigen that T-regulatory cells can “see”, then how can we treat autoimmune disease? We are developing methods to engineer T-regulatory cells that “see” a self-antigen via an unusual mechanism. T-regulatory cells normally “see” self-antigens via noncovalent chemical bonds. The distinguishing feature of our engineered T-regulatory cells is that they “see” self-antigen via a covalent bond. This covalent bond forms between cysteine in the T cell receptor and cysteine in the self-antigen. We think a naturally expressed cysteine-containing self-antigen will enable our engineered T-regulatory cells to “see” an organ affected by autoimmune disease, and thereby perform the function of the missing T-regulatory cells.