HLA matching at the epitope level: the way to go

Human leukocyte antigen (HLA) mismatches are important risk factors for antibody-mediated rejection and transplant failure. With the realization that HLAantibodies recognize epitopes rather than antigens, it has become apparent that donor-recipient compatibility should be assessed at the epitope level. Recent developments have increased our understanding of the structural basis of HLA antigenicity (i.e. the reactivity with specific antibody) and immunogenicity (i.e. the ability to induce an antibody response). HLAMatchmaker is a computer algorithm that considers each HLA antigen as a series of small configurations of polymorphic residues, referred to as eplets, as essential components of HLA epitopes. This chapter addresses the relevance of determining epitope specificities of HLA antibodies in the identification of acceptable mismatches for sensitized patients considered for transplantation. Permissible mismatching for non-sensitized patients aimed to prevent or reduce HLA antibody responses could consider epitope loads of mismatched antigens and the recently developed concepts about the physiochemical basis of immunogenic epitopes and the nonself-self paradigm of eplet immunogenicity.