Polymorphism of the C3b/C4b receptor (CR1): Characterization of a fourth allele

The receptor for C3b/C4b (C3bR or CR1) has an unusual polymorphism in which three codominant alleles determine variants with a large difference in M(r) (160,000, 190,000, or 220,000). We found an individual who has, in addition to the common 190,000 M(r) molecule, a C3bR whose M(r) is 250,000. In this proband and in some members of his family, this novel heterozygous phenotype can be isolated from ¹²⁵I surface-labeled cells by iC3 or iC4 affinity chromatography or by immunoprecipitation with the use of polyclonal or monoclonal anti-C3bR. Relative to the 190,000 M(r) C3bR, E from individuals in this family have 20 to 30% of the total receptor counts in the 250,000 M(r) C3bR. However, on C3bR-bearing leukocytes there is a much larger amount of the 250,000 M(r) C3bR (~60%) relative to the 190,000 M(r) C3bR. Similar to the other three C3bR variants, the M(r) is 5,000 greater on polymorphonuclear cells than on E, and treatment of this new C3bR with endoglycosidase F decreases its M(r) by ~10,000. Therefore, because this variant is inherited and has structural and functional similarities to the other three C3bR, we conclude that this 250,000 M(r) CR1 probably represents a fourth allele.