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.
Menier
C
C
Service de Recherches en Hémato-Immunologie, CEA/DSV/DRM, Hôpital Saint-Louis, IUH, Cedex, Paris, France.
Riteau
B
B
Dausset
J
J
Carosella
E D
ED
Rouas-Freiss
N
N
D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D005333:Fetus / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D020033:Protein Isoforms / Q000276:immunology; D014162:Transfection; D014327:Trophoblasts / Q000276:immunology; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms