C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific
Mary-Pat Stein, … , Carolyn Mold, Terry W. Du Clos
Mary-Pat Stein, … , Carolyn Mold, Terry W. Du Clos
Published February 1, 2000
Citation Information: J Clin Invest. 2000;105(3):369-376. https://doi.org/10.1172/JCI7817.
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Article

C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific

Abstract

C-reactive protein (CRP) is involved in host defense, regulation of inflammation, and modulation of autoimmune disease. Although the presence of receptors for CRP on phagocytes has been inferred for years, their identity was determined only recently. FcγRIa, the high-affinity IgG receptor, binds CRP with low affinity, whereas FcγRIIa, the low-affinity IgG receptor, binds CRP with high affinity. Because the single nucleotide polymorphism in FcγRIIA — which encodes histidine or arginine at position 131 — strongly influences IgG2 binding, we determined this polymorphism’s effect on CRP binding. CRP bound with high avidity to monocytes and neutrophils from FcγRIIA R-131 homozygotes, and binding was inhibited by the R-specific mAb 41H16. CRP showed decreased binding to cells from FcγRIIA H-131 homozygotes (which bind IgG2 with high affinity). However, IFN-γ enhanced FcγRI expression by H-131 monocytes and increased CRP binding. FcγRIIa heterozygotes showed intermediate binding. CRP initiated increases in [Ca2+]i in PMN from R-131, but not from H-131 homozygotes. These data provide direct genetic evidence for FcγRIIa as the functional, high-affinity CRP receptor on leukocytes while emphasizing the reciprocal relationship between IgG and CRP binding avidities. This counterbalance may affect the contribution of FcγRIIA alleles to host defense and autoimmunity.

Authors

Mary-Pat Stein, Jeffrey C. Edberg, Robert P. Kimberly, Erin K. Mangan, Dwaipayan Bharadwaj, Carolyn Mold, Terry W. Du Clos

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Figure 5

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Binding of CRP to FcγRIIIa on NK cells is not detectable. NK cells expre...
Binding of CRP to FcγRIIIa on NK cells is not detectable. NK cells express FcγRIIIa, and 2 allelic forms of this receptor have been described with either phenylalanine (F) or valine (V) at position 176. To determine if CRP can bind to either of these alleles, whole blood from donors homozygous for either F176 or V176 was analyzed. NK cells were identified by a combination of characteristic light scatter properties and CD56 expression. No binding of CRP was detectable on the CD56-positive cells from donors homozygous for either FcγRIIIa allele. (a) CRP binding to F176 allele–bearing donor cells. (b) CRP binding to V176 allele–bearing donor cells. The shaded area is fluorescence with 2C10-FITC alone. (c) Histogram of cells analyzed in a and b. The top right quarter of c, containing CD56+ and CD56+ cells, was selected for analysis by gating.