title: Functional interactions of aglycosylated monoclonal anti-D with Fc gamma RI+ and Fc gamma RIII+ cells.
abstract: Four human monoclonal antibodies (mAb) to the Rh antigen D were produced in aglycosylated forms by culture of B-cell lines in medium containing tunicamycin (Tm-mAb). Erythrocytes sensitized with these or control mAb were compared in U937 rosette and monocyte chemiluminescence assays to determine Fc gamma receptor I (Fc gamma RI)-mediated functional activity, and in lymphocyte rosette and lymphocyte antibody-dependent cell-mediated cytotoxicity (ADCC) assays to study Fc gamma RIII-mediated binding and lysis. Fc gamma RI-mediated interactions with Tm-mAb were greatly reduced compared with control mAb. All Tm-mAb failed to promote ADCC, although lymphocyte rosette formation was unaltered. The anti-D titre of Tm-mAb and their interaction with mAb JL512 (recognizing an epitope in the CH2 domain) were unchanged. These data suggest that glycosylation of IgG is required for CH2 domain interactions with both Fc gamma RI and Fc gamma RIII, but not for CH3 domain interactions with Fc gamma RIII.
authors.affiliation: U.K. Transplant Service, Bristol.
authors.forename: K A
authors.initials: KA
authors.lastname: Leader
authors.forename: B M
authors.initials: BM
authors.lastname: Kumpel
authors.forename: A G
authors.initials: AG
authors.lastname: Hadley
authors.forename: B A
authors.initials: BA
authors.lastname: Bradley
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008163:Luminescent Measurements; D008214:Lymphocytes / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D012397:Rosette Formation
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen