Bootcongres

In kidney transplantation the recognition of mismatched HLA molecules by antibodies limits long term organ survival. Although the occurrence of these antibodies can be prevented by HLA matching, this is not realistic in organ transplantation due to the extent of HLA polymorphisms in the human population. However, it should be feasible to limit the complexity of HLA polymorphisms by only matching the polymorphic structures of the HLA molecule that are exposed at the molecular surface of the patient and donor. Therefore we aimed to couple the immunodominance of HLA class II epitopes and their structural location in the HLA molecule. In our patient cohort we selected patients with antibodies against HLA-DP, HLA-DQ or HLA-DRB3. To develop methodology for epitope discovery in HLA-DRB3 we generated recombinant fusion proteins of DRA and DRB3*01:01 in which we inserted single amino acid substitutions. These fusion proteins, which were checked for correct folding, were used to set up an ELISA detection system. In case of epitope analysis for HLA-DP and HLA-DQ we correlated Luminex single antigen reactivity patterns with peptide alignments. Using these methodologies we identified a new epitope in HLA-DRB3 and we succeeded to pinpoint the potential epitope and its immunodominance in the majority of patients with HLA-DP and HLA-DQ antibodies. 

In conclusion, we demonstrated that the immunodominant epitopes of HLA-DP and HLA-DQ reside in a similar structural element in the HLA class II molecule. In this region, we also identified a new HLA-DRB3 epitope.