BINDING OF MONOMERIC HUMAN-IGG DEFINES AN EXPRESSION POLYMORPHISM OF FC-GAMMA-RIII ON LARGE GRANULAR LYMPHOCYTE NATURAL-KILLER-CELLS

Human PBL express one or more of the three classes of Fc receptors for IgG (Fcgamma receptors I, II, and III). Each type of Fcgamma receptor has a characteristic binding pattern for isotypes of human and mouse IgG. Large granular lymphocyte/NK cells (LGL/NK cells) express the tra nsmembrane form of FcgammaRIII (FcgammaRIIIa) on their surface, wherea s polymorphonuclear neutrophils (PMN) express the glycosyl phosphatidy l inositol-linked receptor that is the product of the FcgammaRIIIB gen e. FcgammaRIII has been reported to have low affinity for monomeric Ig G, regardless of the cell type on which it is expressed. This study de monstrates specific and saturable binding of monomeric human IgG (M-Ig G) to FcgammaRIIIa on LGL/NK cells but not to FcgammaRIIIb on PMN. M-I gG binding revealed an expression polymorphism between individuals, th ose with either high (12,000 to 15,000) or low (4,000 to 7,000) bindin g sites per cell. Both high and low M-IgG-binding LGL/NK cells bound h uIgG1 and IgG3 but did not bind IgG2 or IgG4. The high/low FcgammaRIII A expression polymorphism correlated with the ability of an individual 's LGL/NK cells to perform antibody-dependent cellular cytotoxicity of erythroid cell targets.