HLA-G truncated isoforms can substitute for HLA-G1 in fetal survival.

Pregnancy is considered as an immunologic paradox because the fetus can be viewed as a semiallograft by the mother's immune system. Among the different factors implicated in the maternal-fetal tolerance, a central role has been attributed to HLA-G. The primary HLA-G mRNA is alternatively spliced, encoding four membrane-bound isoforms (HLA-G1, -G2, -G3, and -G4), and three soluble forms (HLA-G5, -G6, and -G7). Whereas HLA-G1 is expressed on trophoblast cells, HLA-G2, -G3, and -G4 isoforms have been only identified as transcripts in trophoblast and term placentas. In this work, we first showed that these HLA-G transcripts are translated into proteins in first trimester cytotrophoblast cells. Then, using a target cell line transfected with HLA-G genomic DNA, we analyzed the functional implication of HLA-G isoforms expression on NK function. Our results show that not only HLA-G1, but also the other HLA-G truncated isoforms, can inhibit NK cytolysis and therefore contribute to immune privilege for the fetus.