KIR2DL1 — inhibitory receptor on uterine NK cell
HLA-Cw4 — C2 group ligand on trophoblast surface
β2-microglobulin — structural component
Bound peptide — antigen fragment
Molecular mechanism of implantation failure
This patient carries KIR-AA — uterine NK cells express only inhibitory receptors. No activating KIRs present.
The embryo is HLA-C2C2. HLA-Cw4 (rose) is a C2 molecule — strongest ligand for KIR2DL1. When KIR2DL1 (blue) docks here, it transmits a halt signal via its ITIM motif.
Consequence: uterine NK cells cannot perform spiral artery remodelling. Placental blood flow insufficient. Two euploid transfers failed.
Fan et al. 2001, Cell · PDB 2DYP · 2.7Å resolution
Moffett et al. 2016, AJRI · Seragen multi-centre n=18,243