eplets

An eplet is a small, functionally relevant epitope on an HLA molecule. In transplantation immunology, eplets are clusters of polymorphic amino acids on the solvent-exposed surface of HLA class I and II proteins that can form an antibody binding site. An eplet represents the minimal set of residues required for antibody recognition, typically a patch of roughly 4–8 amino acids arranged in three dimensions on the protein surface.

Eplets are identified through structural modeling and experimental data and are cataloged to help assess compatibility between donor and recipient. The HLAMatchmaker approach maps donor HLA alleles to their constituent eplets and compares them with the recipient’s antibody specificities to identify mismatched eplets that may give rise to donor-specific antibodies and antibody-mediated rejection risk.

Eplets can be classified as antibody-verified when their reactivity with antibodies has been demonstrated in assays, or as putative/unverified when such evidence is limited. The concept acknowledges that not all eplets are equally immunogenic and that some may be conformationally dependent or influenced by glycosylation and other factors.

Limitations include incomplete knowledge of all immunogenic eplets, structural variability, and differences in assay sensitivity and interpretation. While eplet matching provides finer detail than traditional antigen matching, it remains one tool among many in evaluating transplant compatibility. It is most widely used in kidney transplantation but has informed approaches in other solid organ transplants and in studying donor-specific antibodies.