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The unique structure of the human placenta provides a separation between maternal and fetal tissues and circulations. Although the maternal–fetal proximity is very close, the placenta and the fetus are not rejected by the maternal immune system. Among the various factors implicated in the mother's tolerance of the fetus, a key factor has been attributed to HLA-G molecules, which are expressed by specialized trophoblast cells. By the alternative splicing of its primary mRNA, HLA-G, belonging to Class I MHC molecules, results in four membrane bound (HLA-G1, -G2, -G3, -G4) and three soluble proteins (HLA-G5, -G6, -G7). Which of these HLA-G isoforms are expressed on the cell surface and which are secreted was the aim of our study.

Whereas the generally agreed upon opinion is that the full length HLA-G1 isoform is expressed by extravillous cytotrophoblast cells, the source of soluble HLA-G5 isoform and the expression of all other isoforms in the human placenta is still under debate. However, soluble HLA-G products, which might be present in body fluids, could also come from membrane bound HLA-G1 by shedding; a process, that has been described for classical HLA molecules. HLA-G expression in organs, other than placenta and certain tumors, has not yet been explained convincingly.

Since immunological detection methods crucially depend on the antibodies and preparation techniques used, we investigated HLA-G specific antibodies for their specificity and binding properties. We compared the binding ability of some antibodies on HLA-G1, G2, -G5 transfected cell lines with naturally expressed placental HLA-G molecules. A broad range of methods, from immunolocalization to protein-biochemical and Elisa techniques, were used to clarify which HLA-G isoform is actually expressed in the normal placenta.