FcγRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell FcγRIIIa, independently of the FcγRIIIa-48L/R/H phenotype

• Published in: Blood 1997-08, Vol.90 (3), p.1109-1114
• Main Authors: KOENE, H. R, KLEIJER, M, ALGRA, J, ROOS, D, VON DEM BORNE, A. E. G. K, DE HAAS, M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v90.3.1109

We analyzed a genetic polymorphism of Fcγ receptor IIIa (CD16) that is present on position 158 (Phe or Val) in the membrane-proximal, IgG-binding domain. With a polymerase chain reaction–based allele-specific restriction analysis assay we genotyped 87 donors and found gene frequencies of 0.57 and 0.43 for FcγRIIIA-158F and −158V, respectively. A clear linkage was observed between the FcγRIIIA-158F and −48L genotypes on the one hand and the FcγRIIIA-158V and −48H or −48R genotypes on the other hand (χ2 test; P < .001). To determine the functional consequences of this FcγRIIIa-158V/F polymorphism, we performed IgG binding experiments with natural killer (NK) cells from genotyped donors. All donors were also typed for the recently described triallelic FcγRIIIa-48L/R/H polymorphism. NK cells were treated with lactic acid to remove cell-associated IgG. FcγRIIIaNK158F bound significantly less IgG1, IgG3, and IgG4 than did FcγRIIIaNK-158V, irrespective of the FcγRIIIa-48 phenotype. Moreover, freshly isolated NK cells from FcγRIIIa-158VV individuals carried significantly more cytophilic IgG than did NK cells from FcγRIIIa-158FF individuals. In addition, CD16 monoclonal antibody (MoAb) MEM154 bound more strongly to FcγRIIIa-158V, compared with -158F, again independently of the FcγRIIIa-48 phenotype. The binding of MoAb B73.1 was not influenced by the FcγRIIIa-158V/F polymorphism, but proved to depend solely on the amino acid present at position 48 of FcγRIIIa. In conclusion, the previously reported differences in IgG binding among the three FcγRIIIa-48L/R/H isoforms are a consequence of the linked, biallelic FcγRIIIa-158V/F polymorphism at amino-acid position 158.