HLA-DR antigen on human trophoblast: a review.

Abstract

The mammalian embryo and fetoplacental unit is often likened to a successful semiallograft in the mother. The analogy clarifies little, because the mechanisms of allograft rejection are not understood. However, the concept focuses attention on the major histocompatibility complex (MHC) antigens which were first defined on the basis of allograft rejection. To what extent is the maternal immune system exposed to and stimulated by fetal MHC antigens? The question is central to the understanding of the immune mechanisms of pregnancy. Maternal alloantibodies to fetal class I and class II MHC antigens occur frequently and normally in human pregnancy.l-' demonstrating that fetal alloantigens are not completely separated from the maternal immune system. Alloantibodies can develop during a first pregnancy"; hence maternal alloimmunization is not usually dependent on events at delivery and, in this respect, differs from rhesus isoimmunization. The antibodies bind to placental tissue from where they can be eluted.v" The binding is alloantigen-specific which has led to the concept that the placenta may function as an antibody filter, protecting the fetus against potentially harmful cytotoxic antibodies." Maternal IgG is bound to cells in the chorionic villous stroma and is not found on the syncytiotrophoblast." Maternal alloantibodies have not been documented in all pregnancy sera although this may be only because the methods used for their detection are inadequate. Nevertheless, it has been postulated that they have an essential regulatory function as "blocking" antibodies which protect the fetus from immune rejection." It is then further suggested that failure of alloimmunization leads to pregnancy failure. This may occur where the mother and father share HLA antigens, particularly at the DR locus, and may be a cause of unexplained recurrent first trimester abortion." Even though the postulated mechanisms are completely undefined, trials of therapeutic maternal alloimmunization are underway in an attempt to prevent unexplained recurrent abortion. 10 .