Killer-cell immunoglobulin-like receptor–ligand mismatch

“Killer-cell immunoglobulin-like receptor–ligand mismatch” is not a single molecule or receptor but a genotypic/phenotypic condition describing the absence of a cognate HLA class I ligand for an inhibitory KIR present on natural killer (NK) cells, typically considered in donor–recipient pairs in transplantation. Because KIR and HLA genes segregate independently, a donor (or patient) may express inhibitory KIRs whose ligands are absent in the recipient (or self), enabling NK cells to sense “missing self” and mediate cytotoxicity. This concept is used to model and sometimes select donors for hematopoietic cell transplantation or NK-cell therapy; its clinical impact is context-dependent, with studies showing potential antileukemic effects in some settings and neutral or adverse effects in others.[1][2][3][4] Essential context and supporting details: - KIRs are polymorphic NK-cell receptors that recognize HLA class I molecules; lack of HLA class I ligand on targets (missing-self) can trigger NK cytotoxicity when inhibitory KIRs are not engaged.[1][4] - Because KIR and HLA loci are on different chromosomes and segregate independently, individuals can express inhibitory KIR without the corresponding HLA ligand; in transplantation this creates KIR–HLA receptor–ligand mismatch scenarios.[1][2] - Clinical studies have explored whether inhibitory KIR–HLA receptor–ligand mismatch reduces relapse via enhanced NK activity after autologous or allogeneic transplantation, with evidence of antitumor activity in some contexts.[2][1] - In unrelated cord blood transplantation for AML, analyses found no overall benefit of KIR-ligand matching in 6–7/8 HLA matches, while in 3–5/8 HLA-mismatched cases, KIR-ligand mismatch in the HVG direction associated with higher non-relapse mortality and overall mortality, arguing against selecting units solely on KIR-ligand status in that setting.[3] - Inhibitory KIR–ligand specificities include KIR2DL1 recognizing HLA-C2, KIR2DL2/3 recognizing HLA-C1, and KIR3DL1 recognizing HLA-Bw4; thus, “ligand mismatch” often refers to absence of these epitopes in the counterpart’s HLA repertoire.[4]

Other names

KIR–ligand mismatchKIR–HLA receptor–ligand mismatchKIR/HLA mismatchKIR–ligand incompatibility