Development of donor-specific and non-donor-specific HLA-DP antibodies post-transplant: the role of epitope sharing and epitope matching.

In conclusion, this case provided a unique illustration of de novo production of DSA following transplant from an HLA-A, -B, and -DR matched donor (eliminating the masking effect of these potential mismatches). The antibody generated could be tracked down not only to the allele level of the mismatched HLA antigen but also to the exact epitope that was conceived immunogenic by the recipient. Identifying this epitope also explained the presence of the additional non-donor-specific antibodies (NDSAs) that are actually the same antibody recognizing a shared epitope by multiple HLA-DP alleles. Finally, this information provided valuable information for selecting the most suitable donor for this patient. The concept of shared epitopes was first described by Parham et al. in 1980, and it was revisited recently by Piazza et al. This concept was further developed into a proposal for epitope matching rather than the conventional antigen matching. A simplified algorithm has been developed and implemented by Duquesnoy. The case presented in this manuscript provides a "poster child" example for the role of epitope matching. It is time that the community re-evaluates our nomenclature and scientific reasoning. Current nomenclature stems from historic events that led to the discovery of the HLA system. However, once molecular sequences and 3D structures of the HLA molecules have been elucidated and interactions between the HLA molecules and T-cell receptors have been deciphered, reclassification of the HLA system based on immunogenic epitopes is warranted.