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.