Polymorphism of human erythrocyte C3b/C4b receptor.

Abstract

The human erythrocyte receptor for the major activation fragments of the 3rd and 4th components of complement [C3, C4] (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 MW of 190,000. Type b had a single major band with MW of 220,000, and type c had 2 major bands of MW 190,000 and 220,000. In all 3 types, a minor band accounting for < 25% of the total radioactivity was usually observed at a MW 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 3 types were distinct after reduction and alkylation, although the apparent MW uniformly increased by .apprxeq. 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 2 codominant alleles. In the normal population 2 alleles appear to control expression of HuE-C3bR phenotypes and account for the polymorphism of this integral membrane glycoprotein.