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 semi-allograft by the mother's immune system. Among the differe nt: 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 thre e soluble forms (HLA-GS, -G6, and -G7). Whereas HLA-G1 is expressed on trop hoblast cells, HLA-G2,-G3, and -G4 isoforms have been only identified as tr anscripts in trophoblast and term placentas. In this work, we-first showed that these HLA-G transcripts are translated inco proteins in first trimeste r cytotrophoblast cells. Then, using a target cell line transfected with HL A-G genomic DNA, me analyzed the Functional implication of HLA-G isoforms e xpression on NK function. Our results show that not only HLA-G1, but also t he other HLA-G truncated isoforms, can inhibit NK cytolysis and therefore c ontribute to immune privilege for the fetus. (C) American Society for Histo compatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.