HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells

Non-classical MHC class I molecule HLA-E is the ligand for CD94/NKG2 NK cel l receptors. Surface expression of HLA-E requires binding of specific HLA c lass I leader sequences. The uterine mucosa in early pregnancy (decidua) is infiltrated by large numbers of NK cells, which are closely associated wit h placental trophoblast cells. In this study we demonstrate that trophoblas t cells express HLA-E on their cell surface in addition to the previously r eported expression of HLA-G and HLA-C. Furthermore, we show that the vast m ajority of decidual NK cells bind to HLA-E tetrameric complexes and this bi nding is inhibited by mAb to CD94. Thus, recognition of fetal HLA-E by deci dual NK cells may play a key role in regulation of placentation. The functi onal consequences of decidual NK cell interaction were investigated in cyto toxicity assays using polyclonal decidual NK cells. The overall effect of C D94/NKG2 interaction with HLA-E is inhibition of cytotoxicity by decidual N K cells. However, since decidual NK cells are unable to kill trophoblast ev en in the presence of mAb to MHC class I molecules and NK cell receptors, H LA-E interaction with CD94/NKG2 receptors may regulate other functions besi des cytolysis during implantation.