Reflections on HLA Epitope-Based Matching for Transplantation

Abstract

HLA antibodies are primary causes of transplant rejection; they recognize epitopes that can be structurally defined by eplets. There are many reviews about HLA epitope-based matching in transplantation. This article describes some personal reflections about epitopes including a historical perspective of HLA typing at the antigen and allele levels, the repertoires of antibody-verified HLA epitopes, the use of HLAMatchmaker in determining the specificities of antibodies tested in different assays, and, finally, possible strategies to control HLA antibody responses.

Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation

“…11 Perfect HLA matching of donors and recipients will prevent dnDSA development but at the cost of excluding the majority of potential donors for a recipient in need. 11 Perfect HLA matching of donors and recipients will prevent dnDSA development but at the cost of excluding the majority of potential donors for a recipient in need.…”

“…An eplet is a polymorphic 3Å region on the surface of an HLA antigen that binds to the specificity-determining area of an antibody. 11 Each HLA antigen has a large number of eplets.…”

“…It is the eplet that dictates the antibody specificity, but other regions of the epitope may determine the ability of the antibody to bind to a cell and to initiate an alloimmune response. 11 Perfect HLA matching of donors and recipients will prevent dnDSA development but at the cost of excluding the majority of potential donors for a recipient in need.…”

Donor specific HLA antibodies & allograft injury: mechanisms, methods of detection, manifestations and management

“…Alternatively, it may be worth considering the number of HLA eplet mismatches which has been associated with the risk of dnDSA in lung and kidney transplantation . However, eplets also differ in their immunogenicity according to their position in vivo and their electrophysicochemical properties and it may be that specific eplets are particularly immunogenic . It is likely that these are the eplets which defined the cross‐reactive groups (CREGs) of HLA antigens which were identifiable serologically .…”

Applying genomics in heart transplantation

“…There is a major need for more comprehensive catalogs of polymorphisms across the HLA Class I , II, and wider MHC regions such as the Immuno Polymorphism Database (IPD) which contains a wealth of HLA alleles , although there is still a limited amount of HLA datasets from non‐EA populations. There is an ever‐growing body of clinical data showing that epitope‐based HLA matching is superior to conventional HLA antigen matching for a range of post‐transplant clinical outcomes, and it is likely that these approaches will become a major consideration in clinical D‐R matching in the next few years .…”