Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman’s immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal–fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.