title: HLA-G*0105N null allele encodes functional HLA-G isoforms.
abstract: Expression of the nonclassical HLA class I antigen, HLA-G, is associated with immune tolerance in view of its role in maintaining the fetus in utero, allowing tumor escape, and favoring graft acceptance. Expressed on invasive trophoblast cells, HLA-G molecules bind inhibitory receptors on maternal T lymphocytes and NK cells, thereby blocking their cytolytic activities and protecting the fetus from maternal immune system attack. The HLA-G gene consists of 15 alleles, including a null allele, HLA-G*0105N. HLA-G*0105N presents a single base deletion, preventing translation of both membrane-bound (HLA-G1) and full-length soluble isoforms (HLA-G5) as well as of the spliced HLA-G4 isoform. The identification of healthy subjects homozygous for this HLA-G null allele suggests that the HLA-G*0105N allele may generate other HLA-G isoforms, such as membrane-bound HLA-G2 and -G3 and the soluble HLA-G6 and -G7 proteins, which may substitute for HLA-G1 and -G5, thus assuming the immune tolerogeneic function of HLA-G. To investigate this point, we cloned genomic HLA-G*0105N DNA and transfected it into an HLA-class I-positive human cell line. The results obtained indicated that HLA-G proteins were indeed present in HLA-G*0105N-transfected cells and were able to protect against NK cell lysis. These findings emphasize the role of the other HLA-G isoforms as immune tolerogeneic molecules that may also contribute to maternal tolerance of the semiallogenic fetus as well as tumor escape and other types of allogeneic tissue acceptance.
authors.affiliation: Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Institut d'Hématologie, Hôpital Saint-Louis, Paris 75010, France. teyssier@dsvidf.cea.fr
authors.forename: Magali
authors.initials: M
authors.lastname: Le Discorde
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Danff
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology*; D059951:HLA-G Antigens; D006801:Humans; D007108:Immune Tolerance; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology; D016297:Mutagenesis, Site-Directed; D011247:Pregnancy; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D020298:U937 Cells
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; C420206:HLA-G*01:05N antigen; D020033:Protein Isoforms; D012333:RNA, Messenger; D004247:DNA