Simplified illustration of the mismatched eplets (ME) between recipient and different donors. HLA class I molecules from recipient and 2 donors are shown with 1 membrane-spanning α (α) chain and 1 light chain, beta2-microglobulin (β2m). Each specific HLA molecule consists of a set of eplets on the surface, represented by different shapes. Compared with donor 1, there are more MEs that are only present in the recipients, resulting in 2 MEs in the GVH direction and 0 mismatch in HVG direction. Similarly, donor 2 has extra eplets compared with recipient eplet repertories and the net result will be 3 MEs in the HVG direction and 0 mismatch in GVH direction. MEs could, therefore, be completely different between different haploidentical donors. Additionally, with 1 donor, MEs recognized from the donor perspective (GVH) could be significantly different from that seen from the recipient’s perspective (HVG). The provoked immune response might be consequently differed, depending on the number of ME, the direction of ME, or even the specific types of ME.