International Immunology, Vol. 13, No. 2, 193-201,
February 2001
© 2001 Japanese Society for Immunology
HLA-G1 co-expression boosts the HLA class I-mediated NK lysis inhibition
Service de Recherches en Hémato-Immunologie, CEA-DRM-DSV, and
1 Immunogénétique de la Souris, INSERM U462, Hôpital Saint-Louis, IUH, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
2 Fondation Jean Dausset, 27 rue Juliette-Dodu, 75010 Paris Cedex, France
Correspondence to: Correspondence to:N. Rouas-Freiss
It is now acknowledged that the pattern of HLA-G expression is not restricted to extravillous cytotrophoblast cells, as several studies described HLA-G in HLA class I+ cells, such as thymic epithelial cells, cytokine-activated monocytes and some tumors. In these situations, HLA-G may provide an additional inhibitory signal to escape from NK cell-mediated cytotoxicity. Accordingly, the aim of this study was to define the behavior of HLA-G once it is co-expressed into an HLA-A, -B, -C and -E+ cell line. For this purpose, HLA-G1 cDNA was transfected into an HLA class I+ melanoma cell line which was used as a target towards freshly isolated peripheral blood NK cells. Cytotoxic experiments using either anti-HLA-G1 or anti-HLA-G1 inhibitory receptor mAb show that HLA-G1 boosts the HLA class I-mediated inhibition of polyclonal NK cells through interaction with ILT-2, which appears as the major HLA-G1 inhibitory receptor involved. Nevertheless, HLA-G1 is also able to inhibit the cytolytic activity of an ILT-2– NK clone which otherwise expresses another HLA-G1 inhibitory receptor belonging to the KIR103 gene family. In order to more precisely define the relative role exerted by HLA-G1 versus -E on polyclonal NK cells, antibody-blocking assays were carried out using either anti-HLA class I or anti-CD94/NKG2A. Results demonstrate that in the absence of HLA-G1, the naturally expressed HLA class I-mediated NK inhibition is predominantly exerted by HLA-E through binding with CD94/NKG2A. In contrast, once HLA-G1 is expressed, it becomes the major NK inhibitory ligand.
Keywords: cytotoxicity, human, MHC, NK cells, tolerance
Transmitting editor: J.-F. Bach
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