Human placental HLA-G expression is restricted to differentiated cytotrophoblasts.
Human placental trophoblasts lie at the maternal-fetal interface, a position in which they could play an important role in maternal tolerance of the fetal semi-allograft. Central to this hypothesis is their unusual MHC class I expression: they suppress class Ia production while expressing HLA-G, a class Ib molecule. We investigated human trophoblast HLA-G protein production in vivo and in vitro. We first used a synthetic peptide corresponding to the variable sequence of the alpha 1 domain to produce mAbs that recognized HLA-G. Ab specificity was demonstrated by immunoaffinity purification of a single protein with the same molecular mass (38 kDa) as HLA-G from choriocarcinoma cells. Use of these Abs to stain tissue sections of the maternal-fetal interface containing cytotrophoblasts in all stages of differentiation showed that HLA-G is expressed only by cytotrophoblasts that invade the uterus. Our previous in vitro studies showed that when early-gestation cytotrophoblast stem cells are cultured, they differentiate rapidly along the invasive pathway, as demonstrated by their expression of stage-specific markers. Here we show they also up-regulate HLA-G production. Cytotrophoblasts from term placentas, which have reduced invasive capacity in vitro, also had decreased ability to up-regulate HLA-G protein expression. We detected high levels of HLA-G mRNA in cytotrophoblasts isolated from first- and second-trimester placentas, but only trace amounts in term cells. Taken together, these results suggest that HLA-G production is a critical component of cytotrophoblast differentiation along the invasive pathway.
McMaster
M T
MT
Department of Stomatology, University of California San Francisco 94143, USA.
Librach
C L
CL
Zhou
Y
Y
Lim
K H
KH
Janatpour
M J
MJ
DeMars
R
R
Kovats
S
S
Damsky
C
C
Fisher
S J
SJ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010920:Placenta / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D012333:RNA, Messenger