HLA Epitopes - Are We Ready for Clinical Prime Time? Historic Perspective and Future Needs

A significant barrier to long-term transplant success is the development of de novo donor-specific human leukocyte antigen (HLA) antibodies. The best approach to minimize the risk of developing such antibodies is an HLA identical transplant, but the likelihood of finding such an organ is very low. The alternative is to identify "permissible mismatches" - HLA antigen mismatches that are less likely to induce an immune response. In the past few years, it has become clear that matching at the "epitope level" is the likely solution; however, we are still struggling with how to define HLA epitopes. Herein, we provide a short review of the development of the epitope concept within the HLA field, with the hope that it sheds light on present knowledge. We follow with our personal opinion on where the future is leading us.