Regulation of human natural cytotoxicity by IgG. IV. Association between binding of monomeric IgG to the Fc receptors on large granular lymphocytes and inhibition of natural killer (NK) cell activity.
The regulation of human natural killer (NK) activity by IgG described previously by us depends on the ability of cytophilic molecules of monomeric IgG (mIgG) to inhibit the subsequent killing of NK-sensitive targets. Highly purified NK cells obtained from human peripheral blood are able to directly bind mIgG as well as antigen-complexed IgG through its Fc region. The demonstration that NK cells bear labile cytophilic IgG, a property which usually has been attributed to L cells, indicates that mIgG-induced inhibition of NK activity is mediated by direct interactions between the inhibitory ligand and cytotoxic effector cells. The Fc receptor (FcR) mediating downregulation of NK cytotoxicity appeared to be FcR gamma III, previously found to be selectively expressed on NK cells and granulocytes. In studies of unidirectional cross-inhibition of mIgG binding to NK cells by various anti-CD16 monoclonal antibodies, binding characteristics of mIgG or complexed IgG were similar. Thus, the FcR gamma III for mIgG appear to be indistinguishable from receptors responsible for binding of polymeric IgG on human NK cells. The negative regulation of NK activity by mIgG was not attributable to inhibition of conjugate formation between effector cells and K532 targets, but rather to inhibition of a post-binding event involved in killing of conjugated targets. The data presented suggest that the Fc gamma RIII on human NK cells can either mediate killing against IgG antibody-coated target cells or, upon interaction with cytophilic monomeric ligand in soluble form, induce inhibition of NK activity.
Sulica
A
A
Department of Immunology, Victor Babes Institute, Bucharest, Romania.
Galatiuc
C
C
Manciulea
M
M
Bancu
A C
AC
DeLeo
A
A
Whiteside
T L
TL
Herberman
R B
RB
D000936:Antigen-Antibody Complex / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D017452:Receptors, IgG