Heterogeneity in the ability of IgG1 monoclonal anti-D to promote lymphocyte-mediated red cell lysis.
Thirty-four IgG anti-D human monoclonal antibodies (mAb) derived from 18 donor were assessed for their ability to mediate lysis of D+ red cells by lymphocytes in antibody-dependent cell-mediated cytotoxicity assays. Cell-bound antibody was quantified and the mAb were compared at similar levels of sensitization. The majority (23/31) of IgG1 and all (3/3) IgG3 mAb were ineffective; two donors produced both lytic and non-lytic anti-D mAb. Greater sensitivity was achieved using fluid-phase antibody (as culture supernatants) in the assay than was obtained with pre-sensitized red cells. Minimum levels of 2000 anti-D molecules per cell were required for lysis using pre-sensitized cells. Partial D red cells (DIVa, DVa and DVI) were lysed by three mAb that were lytic with normal D+ cells. There was no relationship between lytic ability and Gm allotype or D epitope specificity of the antibodies. Four mAb to other blood group specificities were tested: two (anti-E and anti-G) were lytic and two (anti-c and anti-Kell) were not lytic. Possible reasons for the heterogeneity of the lytic activity by the mAb are discussed.
Kumpel
B M
BM
U.K. Transplant Service, Bristol, GB.
Leader
K A
KA
Merry
A H
AH
Hadley
A G
AG
Poole
G D
GD
Blancher
A
A
Goossens
D
D
Hughes-Jones
N C
NC
Bradley
B A
BA
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000939:Epitopes; D004912:Erythrocytes / Q000276:immunology; D006384:Hemagglutination; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009000:Monocytes / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D012204:Rh-Hr Blood-Group System