Maternal NK cell recognition of the placenta determines reproductive outcome

About 10 per cent of the burden of disease worldwide is linked to problems of pregnancy, childbirth and infancy, particularly in Sub-Saharan Africa. In the pregnant uterus, specialised NK cells have receptors (KIR) that can bind to fetal HLA-C molecules. Because both KIR and HLA genes are extremely variable, different combinations of maternal KIR and fetal HLA variants characterise each pregnancy.

By comparing these maternal KIR/fetal HLA-C combinations in normal pregnancy to those with pregnancy disorders (such as pre-eclampsia or recurrent miscarriage) in 10,000 mothers and children, including 2,000 in Africa,we will pin down the immune system genes responsible for disorders of pregnancy. We will also use transformative new methods to understand how this NK allo-recognition system between maternal immune cells and fetal cells affects the establishment and development of the placenta and thus, the supply of nutrients and oxygen to the fetus.