Natural-killer cell ligands at the maternal-fetal interface: UL-16 binding proteins, MHC class-I chain related molecules, HLA-F and CD48.
BACKGROUND
In the early stages of human placentation, the decidua is invaded by fetal extravillous trophoblast (EVT) cells. Interactions between EVT cells and local decidual leukocytes are likely to contribute to immunological accommodation of the semi-allogeneic fetus.


RESULTS
Natural-killer group 2 member D (NKG2D) and 2B4 (CD244) are receptors ubiquitously expressed by the distinctive population of CD56 bright, uterine natural-killer cells, which dominate the decidua at the time of implantation. Here, we investigate the UL-16 binding protein (ULBP) and MHC class-I chain related molecule (MIC) ligands of NKG2D, the CD48 ligand of 2B4 and the non-classical HLA class-I molecule, HLA-F, at the maternal-fetal interface of normal pregnancies. For many of these molecules, significant mRNA expression was detected by RT-PCR in decidual and placental tissue throughout gestation. Flow cytometry of isolated cells or immunohistological staining of implantation site sections was then performed. No protein expression of NKG2D ligands or HLA-F could be detected in decidual leukocytes or fetal trophoblast cells from the first trimester. An NKG2D-Fc fusion protein identified no novel ligands for this promiscuous receptor at the maternal-fetal interface. Strong surface protein expression of CD48 by decidual leukocytes but not by trophoblast cells was detected by flow cytometry. Histological staining showed a clear aggregation of CD48(+) cells around transformed spiral arteries of the implantation site.


CONCLUSIONS
We conclude that the role of NKG2D and 2B4 is not focussed on trophoblast recognition in normal pregnancy, but is more likely involved in cross-talk among maternal cells of the placental bed.
Apps
Richard
R
Department of Pathology, University of Cambridge, Cambridge, UK.
Gardner
Lucy
L
Traherne
James
J
Male
Victoria
V
Moffett
Ashley
A
D015703:Antigens, CD / Q000096:biosynthesis*; D000071178:CD48 Antigen; D019002:CD56 Antigen / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000378:metabolism; D058851:GPI-Linked Proteins; D006680:HLA Antigens / Q000096:biosynthesis*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy / Q000276:immunology; D014327:Trophoblasts / Q000378:metabolism
D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D019002:CD56 Antigen; D058851:GPI-Linked Proteins; D006680:HLA Antigens; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C423231:ULBP1 protein, human