Eplet

An eplet is a small, surface-exposed configuration on an HLA molecule that constitutes a functional epitope recognized by antibodies. In immunogenetics and transplantation science, eplets are used to describe minimal antigenic determinants formed by clusters of polymorphic amino acids whose three-dimensional arrangement on the HLA surface can be bound by alloantibodies.

The concept is central to the HLAMatchmaker framework, which maps known eplets onto HLA alleles to assess donor–recipient compatibility beyond broader antigen-level matching. An eplet typically comprises a set of residues—often three to five amino acids—whose spatial arrangement creates an exposed patch on the HLA molecule. Different alleles can share or differ in their eplet makeup, influencing potential antibody reactivity.

Practical use involves comparing donor and recipient HLA types at the eplet level to identify mismatches that might provoke antibody formation. Serologic testing for HLA antibodies, such as single antigen bead assays, can reveal specific antibody reactivities that are interpreted in light of eplet definitions to estimate the risk of alloimmune responses and transplant rejection.

Limitations of the eplet model include its simplification of complex antibody–antigen interactions. Not all eplets are equally immunogenic, and immunogenicity can be influenced by surrounding structural context and conformational dynamics. Mapping eplets relies on structural data and defined consensus sets that can evolve as new information emerges. Despite these caveats, the eplet concept remains a widely used tool for refined HLA matching in transplantation.