Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind to peripheral blood myelomonocytic cells.
The nonclassical MHC class I molecule human histocompatibility leukocyte antigen (HLA)-G is selectively expressed on fetal trophoblast tissue at the maternal-fetal interface in pregnancy. It has long been suggested that HLA-G may inhibit maternal natural killer (NK) cells through interaction with particular NK cell receptors (KIRs). To investigate interactions of HLA-G, we constructed phycoerythrin-labeled tetrameric complexes of HLA-G refolded with a self-peptide. These HLA-G tetramers failed to bind to NK cells and cells transfected with CD94/NKG2 and killer immunoglobulin-like NK receptors. In contrast, HLA-G tetramers did bind to peripheral blood monocytes, staining a CD16(+)CD14(mid) subset with greater intensity. On transfectants, HLA-G tetramers bound to inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors. However, staining in the presence of antibodies reactive with ILT receptors revealed that the interaction of HLA-G tetramers with blood monocytes was largely due to binding to ILT4. These results suggest that the primary role of HLA-G may be the modulation of myelomonocytic cell behavior in pregnancy.
Allan
D S
DS
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
Colonna
M
M
Lanier
L L
LL
Churakova
T D
TD
Abrams
J S
JS
Ellis
S A
SA
McMichael
A J
AJ
Braud
V M
VM
D000818:Animals; D001704:Biopolymers; D002460:Cell Line; D006680:HLA Antigens / Q000737:chemistry / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017452:Receptors, IgG / Q000032:analysis; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D001704:Biopolymers; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C491341:LILRB2 protein, human; D018950:Lipopolysaccharide Receptors; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins