HLA epitope based matching for transplantation

As important risk factors for transplant rejection and failure, HLA antibodies are now recognized as being specific for epitopes which can be defined structurally with amino acid differences between HLA alleles. Donor-recipient compatibility should therefore be assessed at the epitope rather than the antigen level. 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. It includes epitopes on antigens encoded by all HLA-A, B, C, DR, DQ and DP loci as well as MICA. HLA epitopes have two characteristics namely antigenicity, i.e. the reactivity with antibody and immunogenicity, i.e. the ability of eliciting an antibody response. This article addresses the relevance of determining epitope-specificities of HLA antibodies, the effect of epitope structure on technique-dependent antibody reactivity and 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 nonself-self paradigm of epitope immunogenicity.