Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition.
In this study we focused on the structure and expression of the HLA-E, F, and G class I complexes in placental tissue. Structural analysis included an examination of the peptides bound to soluble and membrane forms of the HLA-G complex isolated directly from placenta. An important distinction was observed from HLA-G bound peptides previously isolated from transfectant cells. Thus, the number of distinct moieties bound to placental-derived proteins was substantially lower than that bound to transfectant-derived HLA-G. Indeed, a single peptide species derived from a cytokine-related protein alone accounted for 15% of the molar ratio of HLA-G bound peptide. To further examine HLA-E and its potential to bind peptide, notably that derived from HLA-G, we combined new Abs to examine expression in placental tissues for all the known forms of the nonclassical class I molecules. Whereas membrane HLA-G was found in extravillous trophoblasts, soluble HLA-G was found in all placental trophoblasts, including villous cytotrophoblasts and syncitiotrophoblasts. Further, HLA-E was found in all cells that expressed either form of HLA-G, consistent with HLA-E being complexed with the HLA-G signal sequence-derived nonamer in these cells. Finally, using new reagents specific for HLA-F, a restricted pattern of expression was observed, primarily on extravillous trophoblasts that had invaded the maternal decidua. Comparative staining indicated that HLA-F was on the surface of these cells, defining them as the first to demonstrate surface expression of this Ag and the first cell type identified to express all three nonclassical HLA class I Ags simultaneously.
Ishitani
Akiko
A
Nara Medical University, Kashihara, Nara, Japan. iakiko@naramed-u.ac.jp
Sageshima
Noriko
N
Lee
Ni
N
Dorofeeva
Natalia
N
Hatake
Katsuhiko
K
Marquardt
Hans
H
Geraghty
Daniel E
DE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003656:Decidua / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas; D008024:Ligands; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000276:immunology; D012995:Solubility; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000097625:HLA-E Antigens
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009842:Oligopeptides; D000097625:HLA-E Antigens; C062341:HLA-F antigens