FETAL-MATERNAL TOLERANCE - ROLE OF HLA-G IN PROTECTION OF THE FETUS AGAINST MATERNAL NATURAL-KILLER-CELL ACTIVITY

HLA-G is a non-classical major histocompatibility complex class I mole cule selectively expressed on extravillous trophoblast cells at the fe tal-maternal interface. HLA-G may play an important Pole in maintainin g maternal immune tolerance of the semi-allogenic fetus. In this study , we demonstrate for the first time the protective role of HLA-G durin g pregnancy. Indeed cytotrophoblast cells of the fetus are resistant t o lytic activity by maternal decidual natural Killer cells. In order t o precisely characterize the immunological functions of HLA-G products , we have investigated the protective role of the membrane-bound HLA-G 1 and HLA-G2 isoforms against NK cell cytotoxicity. For this purpose, HLA-G1 and HLA-G2 cDNAs were transfected into the HLA-class I negative human K562 cell line. We demonstrate that both HLA-G1 and HLA-G2 tran sfectants inhibit NK cytolysis observed in peripheral blood from 25 do nors (males and females). This led us to the conjecture that HLA-G is the public ligand for natural killer inhibitory receptors present in a ll individuals.