The HLA-G*0105N null allele induces cell surface expression of HLA-E molecule and promotes CD94/NKG2A-mediated recognition in JAR choriocarcinoma cell line.
HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast cells, and is thought to play a key role in the induction of materno-fetal tolerance during pregnancy. In addition, the HLA-G gene provides a suitable leader sequence peptide capable of binding to HLA-E. However, the existence of placentas homozygous for the HLA-G*0105N null allele suggests that HLA-G1 might not be essential for fetal survival. To investigate whether expression of the HLA-G*0105N allele supports HLA-E cell surface expression, we transfected the HLA-G*0105N gene into JAR trophoblast cells. Flow cytometry analysis showed that HLA-G*0105N-transfected cells express surface HLA-E to a similar extent as the unmutated HLA-G gene, whereas HLA-G1 cell surface expression was undetectable. Using the NKL cell line in a standard (51)Cr release assay, the HLA-E molecules were found to inhibit natural killer lysis, through a mechanism partially dependent on CD94/NKG2A-mediated recognition.
Sala
Frédéric G
FG
Institut National de la Santé et de la Recherche Médicale U 563, Centre de Physiopathologie de Toulouse Purpan, Hôpital Purpan, BP 3028, 31024 Toulouse Cedex 3, France.
Del Moral
Pierre-Marie
PM
Pizzato
Nathalie
N
Legrand-Abravanel
Florence
F
Le Bouteiller
Philippe
P
Lenfant
Françoise
F
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002822:Choriocarcinoma / Q000276:immunology* / Q000378:metabolism; D002860:Chromium Radioisotopes / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097625:HLA-E Antigens
D015703:Antigens, CD; D002860:Chromium Radioisotopes; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C420206:HLA-G*01:05N antigen; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human