Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function.
The nonclassical class I MHC molecule HLA-G is selectively expressed on extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. HLA-G can inhibit the killing mediated by NK cells via interaction with the inhibitory NK cell receptor, leukocyte Ig-like receptor-1 (LIR-1). Comparison of the sequence of the HLA-G molecule to other class I MHC proteins revealed two unique cysteine residues located in positions 42 and 147. Mutating these cysteine residues resulted in a dramatic decrease in LIR-1 Ig binding. Accordingly, the mutated HLA-G transfectants were less effective in the inhibition of NK killing and RBL/LIR-1 induced serotonin release. Immunoprecipitation experiments demonstrated the involvement of the cysteine residues in the formation of HLA-G protein oligomers on the cell surface. The cysteine residue located at position 42 is shown to be critical for the expression of such complexes. These oligomers, unique among the class I MHC proteins, probably bind to LIR-1 with increased avidity, resulting in an enhanced inhibitory function of LIR-1 and an impaired killing function of NK cells.
Gonen-Gross
Tsufit
T
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Achdout
Hagit
H
Gazit
Roi
R
Hanna
Jacob
J
Mizrahi
Sa'ar
S
Markel
Gal
G
Goldman-Wohl
Debra
D
Yagel
Simcha
S
Horejsí
Václav
V
Levy
Ofer
O
Baniyash
Michal
M
Mandelboim
Ofer
O
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D001667:Binding, Competitive / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D003545:Cysteine / Q000235:genetics / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003656:Decidua / Q000166:cytology / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
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; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D003545:Cysteine