title: Involvement of position-147 for HLA-E expression.
abstract: HLA-E functions as an inhibitory signaling molecule of natural killer (NK) cell-mediated cytolysis. However, the cell surface expression of HLA-E molecules is quite restricted because of the limited repertoire of binding peptide sequences, such as signal peptides of other HLA molecules, especially on xenogeneic cells. In this study, we successfully determined that position-147 is an important amino acid position for cell surface expression by producing point substitutions. For further studies concerning transplantation therapy, the point substitution, Ser147Cys, that resulted in a single atom change, oxygen to sulfur, designated as HLA-Ev(147), led to a much higher expression on the human and pig cell surface and a greater inhibitory function against human NK cells than wild type HLA-E in an in vitro model system of pig to human xenotransplantation. Consequently, HLA-Ev(147) might be a promising alternative gene tool for future transplantation therapy such as xenotransplantation.
authors.affiliation: Division of Organ Transplantation, Department of Molecular Therepeutics, Osaka University Graduate School of Medicine, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Matsunami
authors.forename: Tamiko
authors.initials: T
authors.lastname: Kusama
authors.forename: Eiji
authors.initials: E
authors.lastname: Okura
authors.forename: Ryota
authors.initials: R
authors.lastname: Shirakura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Miyagawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism
chemical_list: D006680:HLA Antigens