Polymorphism of human erythrocyte C3b/C4b receptor

The human erythrocyte receptor for the major activation fragments of the third and fourth components of complement (HuE-C3bR) was isolated from individual donors. Erythrocytes were surface labeled with ¹²⁵I and solubilized in Nonidet P-40. HuE-C3bR was purified by using C3-Sepharose affinity chromatography and analyzed by autoradiography of NaDodSO₄/polyacrylamide gels. Three distinct receptor patterns were demonstrated. Type a had a single major band with M(r) of 190,000, type b had a single major band with M(r) of 220,000, and type c had two major bands of M(r) 190,000 and 220,000. In all three types, a minor band accounting for <25% of the total radioactivity was usually observed at a M(r) 15,000 greater than that of each major band. Identical autoradiographic patterns were obtained by affinity chromatography using methylamine-inactivated C4-Sepharose or by immunoprecipitation of solubilized membranes with a monoclonal antibody against HuE-C3bR. All three types were distinct after reduction and alkylation, although the apparent M(r) uniformly increased by ≃30,000. Characterization of HuE-C3bR types in 33 unrelated individuals demonstrated that 23 had type a, 1 had type b, and 9 had type c. Family studies provide evidence for transmission by two codominant alleles. Thus, in the normal population two alleles appear to control expression of HuE-C3bR phenotypes and account for the polymorphism of this integral membrane glycoprotein.