Hiding in Plain Sight—A New Look at HLA Epitopes: A Case Report

“Epitope matching” has become a buzz word in solid organ transplantation. Its goal is to improve matching between donor and recipient, to minimize risk for antibody‐mediated rejection and to reduce sensitization associated with graft failure. Current software allows identification and enumeration of amino acid sequence mismatches in the form of HLA eplets; however, “eplets” and “epitopes” are not interchangeable terms, and the understanding of what contributes to the antigenicity and immunogenicity of HLA B cell epitopes is still very limited and inadequate. In fact, we still do not know what constitutes an HLA epitope or how to define it in a clinically useful way. To allow for judicious implementation of epitope matching, it is critical to explore the full spectrum of factors that affect allorecognition. In exploring antibody‐binding patterns, we have uncovered a potential tool—currently hidden in plain sight—that may shed light on some aspects of epitope characteristics.