The interaction of murine IgG subclass proteins with human monocyte Fc receptors.
The use of murine monoclonal antibodies in the immunotherapy of human disease has prompted interest in the interactions of murine IgG with Fc receptors (FcR) expressed on human effector cells. We examined the heterocytophilic interactions between monomeric murine IgG subclass proteins and the FcR expressed on human monocytic cells (peripheral blood monocytes and interferon (IFN)-gamma-induced U937 cells). All four murine IgG2a antibodies and both murine IgG3 antibodies that were tested bound to human monocyte FcR with high affinity (10(8) to 10(9) M-1). By contrast, the affinities of four murine IgG1 and four IgG2b monomers were 100-fold to 1000-fold lower than the affinity of the human IgG1-FcR interaction. A 68,000 to 72,000 dalton protein was isolated by affinity chromatography from blood monocytes and from IFN-gamma-induced U937 cells on murine IgG2a, IgG3, and human IgG immunoadsorbents. In binding assays with IFN-stimulated U937 cells, murine IgG2a and IgG3 antibodies showed complete cross-blocking with a human IgG1 myeloma protein, indicating that murine and human IgG interact with the same population of Fc-binding proteins. No evidence for heterogeneity of cross-reactive FcR was observed. The ability of murine IgG2a and IgG3 monomers to compete with human IgG1 monomers for binding to human monocyte FcR suggests the potential usefulness of antibodies of these isotypes in the immunotherapy of diseases in which monocyte- or macrophage-mediated, antibody-dependent cellular cytotoxicity may play a role in the modification or remission of disease.
Lubeck
M D
MD
Steplewski
Z
Z
Baglia
F
F
Klein
M H
MH
Dorrington
K J
KJ
Koprowski
H
H
D000818:Animals; D000915:Antibody Affinity; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002460:Cell Line; D003429:Cross Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism*; D017452:Receptors, IgG
D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D007371:Interferon-gamma