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Polymorphism of the C3b/C4b receptor (CR1): characterization of a fourth allele
Insights
Researchers discovered a novel C3b/C4b receptor (C3bR) variant with a molecular weight of 250,000. This finding suggests a fourth allele for the C3bR gene, expanding our understanding of complement receptor diversity.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- The complement system plays a crucial role in innate immunity.
- The C3b/C4b receptor (C3bR or CR1) exhibits known polymorphism with three alleles.
- These alleles result in variants with molecular weights of 160,000, 190,000, and 220,000.
Purpose of the Study:
- To investigate a novel C3bR variant identified in a family.
- To characterize the structural and functional properties of this new C3bR variant.
- To determine if this variant represents a new allele of the C3bR gene.
Main Methods:
- Surface iodination of cells.
- Isolation of C3bR variants using iC3 or iC4 affinity chromatography.
- Immunoprecipitation with polyclonal and monoclonal anti-C3bR antibodies.
- Analysis of molecular weight (Mr) differences and glycosidase treatment.
Main Results:
- A novel C3bR variant with an Mr of 250,000 was identified in a proband and family members.
- This 250,000 Mr C3bR variant was isolated using affinity chromatography and immunoprecipitation.
- Leukocytes showed a higher proportion (approximately 60%) of the 250,000 Mr C3bR compared to erythrocytes (20-30%).
- The Mr of the new variant was approximately 5,000 higher on polymorphonuclear cells than erythrocytes.
- Endoglycosidase F treatment reduced the Mr by approximately 10,000, indicating glycosylation.
Conclusions:
- The 250,000 Mr C3bR variant is inherited and exhibits structural and functional similarities to known C3bR variants.
- This novel variant likely represents a fourth codominant allele for the C3bR gene.
- The findings expand the known allelic diversity of the C3bR/CR1 receptor.
Abstract:
The receptor for C3b/C4b (C3bR or CR1) has an unusual polymorphism in which three codominant alleles determine variants with a large difference in Mr (160,000, 190,000, or 220,000). We found an individual who has, in addition to the common 190,000 Mr molecule, a C3bR whose Mr 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 Mr C3bR, E from individuals in this family have 20 to 30% of the total receptor counts in the 250,000 Mr C3bR. However, on C3bR-bearing leukocytes there is a much larger amount of the 250,000 Mr C3bR (approximately 60%) relative to the 190,000 Mr C3bR. Similar to the other three C3bR variants, the Mr is 5,000 greater on polymorphonuclear cells than on E, and treatment of this new C3bR with endoglycosidase F decreases its Mr by approximately 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 Mr CR1 probably represents a fourth allele.