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J. Exp. Med., Volume 189, Number 7, April 5, 1999 1149-1156

Tetrameric Complexes of Human Histocompatibility Leukocyte Antigen (HLA)-G Bind to Peripheral Blood Myelomonocytic Cells

By David S.J. Allan,* Marco Colonna,Dagger Lewis L. Lanier,§ Tatyana D. Churakova,§ John S. Abrams,§ Shirley A. Ellis,parallel Andrew J. McMichael,* and Veronique M. Braud*

From the * Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom; Dagger  Basel Institute for Immunology, Basel CH-4005, Switzerland; § DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304; and the parallel  Institute for Animal Health, Compton RG20 7NN, United Kingdom

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+CD14mid 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.

Key words: immunoglobulin-like transcript;  monocyte;  natural killer cell;  CD94;  killer immunoglobulin-like receptor


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