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.

Keywords: HLA; antibody; epitope; eplet; mismatch acceptability.

Figure 1

Three models of structural HLA class I epitope. The HLA molecule has three components: HLA chain (pink), β2-microglobulin (blue), and the bound peptide (green). The centrally located eplet (in pink) interacts with CDR-H3. Residues within a 15-Å radius are colored yellow and include configurations (in oval circles) that make contact with other CDRs on heavy chain (H1 and H2) and light chain (L1, L2, and L3). (A–C) reflect three different epitope locations on the molecule.