title: Human Fc gamma RIII (CD16). Isoforms with distinct allelic expression, extracellular domains, and membrane linkages on polymorphonuclear and natural killer cells.
abstract: Human Fc gamma RIII (CD16), a low-affinity receptor expressed on several different cell types, has a polymorphism on polymorphonuclear cells (Fc gamma RIIIPMN) identified by the NA1 and NA2 markers. Inasmuch as this polymorphism has functional consequences, an understanding of the structural biology of Fc gamma RIII may provide important insight into receptor function. We analyzed Fc gamma RIIIPMN by SDS-PAGE and found that receptor from individuals allotyped for either NA1 or NA2 contained only one protein after removal of N-linked glycosylations (19 and 21 kDa respectively) whereas receptor from NA1/2 individuals contained both bands. Because some reports indicate that digestion of Fc gamma RIII on NK cells (Fc gamma RIIINK) with N-glycanase also results in two bands on SDS-PAGE, we investigated Fc gamma RIIINK to explore the possibility of a corresponding allelic polymorphism in this receptor. Contrary to expectation, Fc gamma RIIINK from all donors irrespective of their NA allotype contained two bands (20 and 24 kDa) on SDS-PAGE after deglycosylation. In addition, those distinct epitopes on the extracellular domain of Fc gamma RIIIPMN found with mAb B73.1 and CLB gran 11 in association with the NA allotypic differences are expressed (or not expressed) on Fc gamma RIIINK independent of donor NA allotype. Fc gamma RIIIPMN and Fc gamma RIIINK differ at the protein level as they have different m.w. (glycosylated and deglycosylated), different epitopes in the extracellular domain (not attributable to tissue-specific glycosylation), and differential expression of the NA allelic protein polymorphism. Although the membrane anchor of Fc gamma RIIIPMN is a phosphatidylinositol-specific phospholipase C sensitive glycosyl-phosphatidylinositol linkage, Fc gamma RIIINK is insensitive to phosphatidylinositol-specific phospholipase C. However, a form of Fc gamma RIIINK is released from NK cells upon incubation at 37 degrees C. Thus, the basis for the two bands in Fc gamma RIIINK after N-linked deglycosylation is neither coexpression of two molecular isoforms with different membrane anchors nor an identifiable allelic polymorphism in m.w. restricted to Fc gamma RIIINK (p less than 10(-6)). The differences between the two receptors indicate that, independent of cell anchor type, PMN and mononuclear cells must have different molecular isoforms. The allelic variants, different isoforms, alternative anchor mechanisms and release processes provide for an extensive genetic and regulatory diversity in Fc gamma RIII function.
authors: Hospital for Special Surgery, Cornell University Medical College, New York 10021.
authors: J C
authors: JC
authors: Edberg
authors: P B
authors: PB
authors: Redecha
authors: J E
authors: JE
authors: Salmon
authors: R P
authors: RP
authors: Kimberly
mesh_terms: D000483:Alleles; D000943:Antigens, Differentiation / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism; D006026:Glycoside Hydrolases; D017261:Glycosylphosphatidylinositols; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011110:Polymorphism, Genetic; D011961:Receptors, Fc / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG
chemical_list: D000943:Antigens, Differentiation; D000939:Epitopes; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011961:Receptors, Fc; D017452:Receptors, IgG; D006026:Glycoside Hydrolases; C020668:glycanase