Department of Pathology

Dr Mike Clark

Research description

Antibodies are a major serum protein made by the B-cells of the body's immune system in response to infection. Within an individuals blood, antibodies occur in different forms known as isotypes, and they also show sequence variation within the population as a result of differences in allotype. The role for antibodies in the immune system is to target infectious agents such as viruses, bacteria and parasites and to trigger their destruction or removal through activation of the complement cascade or through binding to and triggering of Fc receptors expressed by blood cells such as monocytes, neutrophils, basophils, eosinophils and K-cells.

Our aim is to try to understand the precise structural requirements for the binding and activation of complement and Fc receptors by individual antibody isotypes and allotypes. We have been investigating these functions using sets of recombinant antibodies matched for identical specificities. Studies have concentrated on the functions of antibodies in association with human effector mechanisms. We have revealed striking variation between antibodies which differ by both isotype and allotype and in several cases we have identified sequences within the molecule which are critical for such functional differences. These basic findings are being put into practice in the design of better recombinant antibodies for potential clinical use in human therapy. One success in this area has been the regulatory approval in 2001 of the antilymphocytic leukaemia antibody called alemtuzumab (CAMPATH®).

Currently we have several collaborations in progress looking at different therapeutic applications of our knowledge. In collaboration with Dr Lorna Williamson, Cambridge University, Division of Transfusion Medicine, we are studying recombinant RhD and HPA-1a antibodies and their potential use in treating alloimmune disorders of red blood cells and of blood platelets during pregnancy. Another collaboration is with Professor Farouk Shakib, University of Nottingham, where we are deriving recombinant antibodies that may have therapeutic potential in the treatment of IgE mediated allergies.