Responsiveness for mouse IgG2b antibodies to the human alpha/beta T-cell receptor/CD3 complex: evidence for genetic determination and low grade antibody cross-linking not mediated by known Fc gamma receptors.
Mouse IgG2a and IgG3 antibodies directed to the human T-cell receptor/CD3 complex stimulate peripheral blood mononuclear cells in almost all individuals. By contrast, responder and non-responder individuals exist for the stimulatory effect of mouse IgG1 and IgG2b antibodies. Whereas responsiveness to IgG1 antibodies is rather frequent (60-70%) and is known to be determined by an Fc gamma RII polymorphism on the accessory cells, little is known about the underlying factors of the rare (6%) IgG2b responsiveness. In this study it is shown that (1) IgG2b responsiveness is genetically determined with a dominant pattern of inheritance; (2) IgG2b responsiveness is determined by a radioresistant feature of responder accessory cells which can be substituted by artificial cross-linking, but not by IL-1 beta or IL-2; (3) stimulation of peripheral blood mononuclear cells of an IgG2b responder by IgG2b antibodies requires rather high antibody concentration compared with stimulation by IgG2a antibodies; (4) the stimulation leads to proliferation and IL-2 receptor expression, but no measurable IL-2 production; (5) antibody binding to known Fc gamma receptors (Fc gamma RI, Fc gamma RII, Fc gamma RIII) is not involved in the stimulatory effect of the IgG2b antibodies in responders. These results demonstrate that responsiveness to IgG2b antibodies against the TcR/CD3 complex depends on a genetically determined feature of accessory cells that is not identical with any of the known Fc gamma receptors. Most likely, the stimulatory effect observed in IgG2b responders is explained by a low grade cross-linking of the antibody by a not yet identified polymorphic structure on the surface of accessory cells.
Schlitt
H J
HJ
Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule, Hannover, Germany.
Schwinzer
R
R
Wonigeit
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D066298:In Vitro Techniques; D051379:Mice; D010375:Pedigree; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011961:Receptors, Fc