title: HLA-G1 co-expression boosts the HLA class I-mediated NK lysis inhibition.
abstract: 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.
authors.affiliation: Service de Recherches en Hémato-Immunologie, CEA-DRM-DSV, Hôpital Saint-Louis, IUH, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France.
authors.forename: B
authors.initials: B
authors.lastname: Riteau
authors.forename: C
authors.initials: C
authors.lastname: Menier
authors.forename: I
authors.initials: I
authors.lastname: Khalil-Daher
authors.forename: S
authors.initials: S
authors.lastname: Martinozzi
authors.forename: M
authors.initials: M
authors.lastname: Pla
authors.forename: J
authors.initials: J
authors.lastname: Dausset
authors.forename: E D
authors.initials: ED
authors.lastname: Carosella
authors.forename: N
authors.initials: N
authors.lastname: Rouas-Freiss
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015703:Antigens, CD; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015234:HLA-A Antigens / Q000096:biosynthesis; D015235:HLA-B Antigens / Q000096:biosynthesis; D015236:HLA-C Antigens / Q000096:biosynthesis; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism; D054340:Receptors, KIR; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097625:HLA-E Antigens
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D000097625:HLA-E Antigens; C105299:LILRB1 protein, human