Regulation of human natural cytotoxicity by IgG--I. Characterization of the structural site on monomeric IgG responsible for inhibiting natural killer cell activity.
Inhibition of human natural killer (NK) cell activity upon exposure of peripheral blood lymphocytes (PBL) to IgG in monomeric form (mIgG) was found to be dose-, time- and temp-dependent. PBL incubated for 2 hr at 37 degrees C in the presence of myeloma protein of a certain class or subclass had a significant reduction of their NK activity when exposed to IgG, but not to IgM or IgD, and the IgG-induced inhibition of NK cells was observed only when IgG1 or IgG3 paraproteins were used. IgG3 isolated from normal serum had a higher inhibitory property than that of total mIgG. The cytophilic activity of the IgG molecules was confined entirely to the Fc region and seemed to be localized in the CH3 domain, since human and rabbit Facb fragments had a reduced ability to inhibit NK activity. When synthetic peptides representing various sequences of the human gamma-chain were tested for inhibition of NK activity, only treatment of effector cells with a peptide comprising the sequence Tyr407-Arg416 of the CH3 domain showed a reduction of NK cell function comparable to the inhibition obtained following incubation of cells in the presence of mIgG. However, on a molar basis, this peptide was 20 times less active than mIgG. In contrast, peptides derived from sequences in the CH2 domain lacked this inhibitory capacity. Our data indicate that the structural site responsible for inhibiting NK cell activity is located in the C-terminal domain of the IgG molecule.
Gherman
M
M
Department of Immunology, Babes Institute, Bucharest, Romania.
Manciulea
M
M
Bancu
A C
AC
Sulica
A
A
Stanworth
D R
DR
Herberman
R B
RB
D000595:Amino Acid Sequence; D000920:Antibody-Dependent Cell Cytotoxicity; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007136:Immunoglobulins; D010446:Peptide Fragments