title: Binding of sialyl Lewis X antigen to lectin-like receptors on NK cells induces cytotoxicity and tyrosine phosphorylation of a 17-kDa protein.
abstract: BACKGROUND
  Natural killer (NK) cells mediate cytotoxicity through cell-surface receptors including lectin-like receptors. We have investigated whether sialyl Lewis X (sLe(X)) antigen, Neu5Acalpha2,3Galbeta1,4(Fucalpha1,3) GlcNAc-R, can bind to the lectin-like receptors on human NK-derived KHYG cells, using transferrin secreted by human hepatoma-derived HepG2 cells (Hep-TF), whose N-glycans are rich in alpha1,3-fucosylated bi-, tri-, and tetra-antennary type complexes, and commercially available human transferrin (Nor-TF), which is comprised of bi-antennary N-glycans without alpha1,3-fucosylation.
  
  
  RESULTS
  High sLeX-expressing erythroleukemia-derived K562 cells isolated from fucosyltransferase-3-transfected cells were 2.5-fold more susceptible than wild-type K562 cells to KHYG cells. Fluorescein isothiocyanate (FITC)-labeled Hep-TF bound 1.8-fold more strongly to KHYG cells than did FITC-labeled Nor-TF; the binding was suppressed by treatment with anti-NKG2D, anti-NKG2C, anti-CD94 and anti-CD161 antibodies. FITC-labeled Hep-TF bound more strongly to human monocyte-derived U937 cells transfected with NKG2D and CD94 than to wild-type U937 cells. Moreover, tyrosine phosphorylation of a 17-kDa protein in the KHYG cells was enhanced by incubation on a Hep-TF coated plate and treatment with an anti-NKG2D antibody, but not by a Nor-TF coated plate and an anti-CD94 antibody.
  
  
  CONCLUSIONS
  The interaction of sLe(X) antigen with lectin-like receptors on NK cells induces cytotoxicity that is mediated through a tyrosine-phosphorylated 17-kDa protein.
authors.affiliation: Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. koji@phar.toho-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Higai
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ichikawa
authors.forename: Kojiro
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology*; D016256:Lewis X Antigen / Q000276:immunology*; D008024:Ligands; D008970:Molecular Weight; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K; D019000:Phosphotyrosine / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014168:Transferrin / Q000378:metabolism
chemical_list: C400041:CLEC2D protein, human; C527059:KLRC2 protein, human; C527085:KLRK1 protein, human; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014168:Transferrin; D019000:Phosphotyrosine; D005647:Fucosyltransferases