Human large granular lymphocytes express high affinity receptors for murine monoclonal antibodies of the IgG3 subclass.
We have evaluated the ability of murine monoclonal antibodies to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) by human lymphoid cells. Purified large granular lymphocytes (LGL) and interleukin 2-dependent cloned LGL lines having a CD2+/CD16+/CD3- phenotype were tested as effector cells in an ADCC assay by using a family of IgG isotype switch variant anti-Thy-1.1 antibodies against 51Cr-labeled Thy-1.1+ murine SL2 thymoma target cells, a system in which human cells have no spontaneous cytotoxicity. Cytotoxicity was greatest when using the IgG3, followed in rank order by the IgG2a and IgG2b. No cytotoxicity was observed with the IgG1 antibody. Because the antigen-binding regions of the antibodies are identical, the differences in cytotoxicity directly reflect the relative affinity of LGL Fc receptors for each antibody isotype.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000920:Antibody-Dependent Cell Cytotoxicity; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes; D008214:Lymphocytes / Q000145:classification / Q000378:metabolism*; D051379:Mice; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011961:Receptors, Fc; D017452:Receptors, IgG