Histocompatibility

AbstractHuman leukocyte antigen (HLA) molecules are the most important histocompatibility antigens, due to their genetic polymorphism and their key role in peptide antigen presentation and T-cell alloreactivity. While full matching for the most relevant HLA loci had been regarded as a prerequisite for successful transplantation until recently, the introduction of posttransplant cyclophosphamide (PTCy) as immune prophylaxis has also allowed successful transplantation across multiple HLA mismatches, thus also enabling access to transplantation for patients without a fully compatible donor. The rules governing high-risk/nonpermissive HLA mismatches, identified in the past as immunopeptidome overlaps, expression levels, and predicted indirectly recognized HLA epitopes (PIRCHEs), will have to be redefined in the PTCy area to further improve patient outcomes.