A critical look at HLA-G

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class-I molecule that was found to be expressed by placental trophoblast cells 20 years ago. Because trophoblast forms the physical interface between fetus and mother, HLA-G might play a role in maternal immunological accommodation of the semi-allogeneic fetus. Despite a mounting number of publications, there is still no consensus on many aspects of HLA-G, including its tissue distribution and receptor binding. Here we critically review the literature and suggest why some of this controversy has arisen and how it might be resolved. We do conclude that the evidence for trophoblast HLA-G stimulating leukocyte immunoglobulin-like receptor B1 receptors on decidual leukocytes is compelling. These findings suggest how a fetal molecule might influence the local maternal immune response.