The major limitation of current assessment of HLA immunogenicity is that all donor HLA within a locus are assigned equal weight despite potential differences in their immunogenic potential. We have been using amino acid sequence and physicochemical analyses of HLA proteins and structural information obtained from X-ray crystallography to identify donor HLA that are likely to be tolerated by the immune system of a particular recipient as opposed to those that may increase the risk of rejection. We have set up an interdisciplinary approach that brings together concepts and methods from structural and computational biology, genetics and medicine, using a combination of in silico, in vitro and in vivo approaches to assess the risk of development (and to enable detection) of cellular (T-cell) and humoral (B-cell) alloimmune responses after transplantation. This work is underpinned by analyses of large clinical datasets to guide and validate our novel methods. Our research is supported by well-established collaborations with NHS Blood and Transplant, Eurotransplant and other international partners (e.g. University of Kiel in Germany; University of Manitoba in Canada; European Bioinformatics Institute in Cambridge).
We have developed software to predict HLA immunogenicity that are freely available below:
