title: HLA-G recognition by human natural killer cells. Involvement of CD94 both as inhibitory and as activating receptor complex.
abstract: The lack of classical human histocompatibility leukocyte antigen (HLA) molecules in human placenta prevents the recognition and lysis by maternal T lymphocytes but poses the problem of susceptibility to natural killer (NK) cell-mediated lysis. The nonclassical HLA class I molecule HLA-G may mediate protection from NK cells. NK cells are known to express a number of HLA class I-specific inhibitory receptors. These include members of the immunoglobulin (Ig) superfamily (p58, p70, p140), characterized by a defined allele specificity, and CD94/NKG2A with a broad specificity for different HLA class I molecules. We analyzed a series of NK cell clones derived from normal peripheral blood expressing different NK receptors (NKR). Clones were analyzed for their cytolytic activity against the HLA class I-negative 221 cell line either untransfected or transfected with HLA-G (221/G) or other informative alleles, as control. All clones expressing CD94/NKG2A [as identified by the Z199 monoclonal antibody (mAb)] displayed a markedly reduced cytolytic activity against 221/G. Moreover, mAb directed to the CD94/NKG2A complex completely restored target cell lysis. Among NKG2A-negative NK clones, different functional patterns could be detected. Clones expressing inhibitory receptors belonging to the Ig superfamily lysed 221/G target cells with equal or higher efficiency than untransfected 221 cells. These data indicated that p58, p70 and p140 do not function as HLA-G-specific inhibitory NKR, and that HLA-G-specific activating NKR also exist. Further analysis indicated that in these clones (characterized by the CD94+/NKG2A- phenotype) mAb specific for CD94, but not for the other NKR, reversed the activating effect. Infrequent clones were also isolated that, in spite of the lack of CD94/NKG2A, displayed HLA-G specificity, thus suggesting the existence of a different, still unknown NKR.
authors.affiliation: Istituto Scientifico Tumori and Centro Biotecnologie Avanzate, Genova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pende
authors.forename: S
authors.initials: S
authors.lastname: Sivori
authors.forename: L
authors.initials: L
authors.lastname: Accame
authors.forename: L
authors.initials: L
authors.lastname: Pareti
authors.forename: M
authors.initials: M
authors.lastname: Falco
authors.forename: D
authors.initials: D
authors.lastname: Geraghty
authors.forename: P
authors.initials: P
authors.lastname: Le Bouteiller
authors.forename: L
authors.initials: L
authors.lastname: Moretta
authors.forename: A
authors.initials: A
authors.lastname: Moretta
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C497869:KLRD1 protein, human; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic