Special organization of the HLA-G protein on the cell surface.
The human leukocyte antigen G (HLA-G) molecule possesses unique properties such as low polymorphism and restricted distribution mainly to the extravillous cytotrophoblast (EVT) cells. The EVT cells vigorously penetrate into the maternal decidual tissues and are found in contact with maternal lymphocytes, mainly with natural killer (NK) cells. The HLA-G molecule inhibits the effector function of maternal NK cells via interaction with the KIR2DL4 and the ILT-2 inhibitory NK receptors. Previously, we have demonstrated that complexes of the HLA-G protein are expressed on the cell surface. We reported that these complexes are formed due to the presence of two unique cysteine residues located at positions 42 and 147. Finally, we demonstrated that efficient binding and function of ILT-2 is dependent on the presence of HLA-G complexes on the cell surface. Here we expand the significance of these observations by revealing that complexes of HLA-G are present on the cell surface using different assays and cell lines and further demonstrate that complexes of HLA-G might be present in a soluble form after interaction with ILT-2. Therefore, the HLA-G molecule has developed a special mechanism to increase the avidity of NK receptors to the HLA-G molecule, which provides better protection for the fetus from maternal NK rejection.
Gonen-Gross
Tsufit
T
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gazit
Roi
R
Achdout
Hagit
H
Hanna
Jacob
J
Mizrahi
Sa'ar
S
Markel
Gal
G
Horejsí
Václav
V
Mandelboim
Ofer
O
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019556:COS Cells; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology*; D002522:Chlorocebus aethiops; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012995:Solubility; D014162:Transfection
D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins