A major barrier in solid organ transplantation is the development of alloantibodies against HLA expressed on donor tissue. Such alloantibodies may preclude transplantation from proceeding, whereas their development after kidney, pancreas, heart and lung transplantation is a major cause of graft loss. However, there is uncertainty regarding the pathogenic potential of alloantibodies detected with currently available techniques limiting our ability to assess the immunological risk associated with a particular transplant and to intervene early before irreversible graft injury is established.
To address these limitations, our research examines the interaction of alloantibodies with HLA at the molecular level and aims to assess the capacity of alloantibodies to activate cellular pathways that lead to organ injury. We have established a multidisciplinary approach that utilises experimental structure determination methods, computational techniques (e.g. structure prediction and molecular dynamics simulations) and in vitro biosensor assays to study alloantibody-HLA interactions that mediate different effector functions. Moreover, in collaboration with Professor Knowles at the Department of Chemistry in Cambridge, we are developing a novel microfluidic platform to enable rapid characterisation of alloantibody-HLA interactions in a quantitative manner and under native conditions directly in patient sera.