Abstract

John Trowsdale Research

The human major histocompatibility complex (MHC) encodes the most polymorphic proteins in the human genome and is associated with more diseases than any other region. Unravelling this complex of human loci, from sequence to function, will help to understand autoimmune diseases such as diabetes, multiple sclerosis and arthritis. The class I and class II molecules encoded by the MHC play a pivotal role in alerting the rest of the immune system to disease by interacting with receptors on T cells. A major part of our work concerns these molecules. Other genes embedded in the MHC provide additional clues to mechanisms of immune recognition and we are studying the functions of some of them, including MOG and BTN .

Further information on the state of health of a cell is provided by interaction of MHC class I molecules with other receptors, on natural killer (NK) cells. Like some MHC genes, the NK receptors are part of extensive gene families. They are involved in activating, or inhibiting NK cells and some T cells. We are studying the organisation of the NK-receptor gene families, their polymorphism and association with disease, particularly in relation to interaction of the receptors with different MHC class I molecules.