Different HLA antigen associations for the functionally active and inactive products of the complement C4F 1 allele

Abstract

The genetic polymorphism of the fourth component of human complement. C4, was studied in 945 unrelated Caucasian individuals. A third allele of the C4F (Rodgers) locus, termed C4F 1 was demonstrated. This allele is characterized using immunofixation electrophoresis, by the presence of an additional fast-moving anodal band of C4 which distinguishes it clearly from the common C4F variant. The allelic frequencies fit the Hardy-Weinberg equilibrium assuming three alleles at the C4F locus: C4F, C4f 0, and C4F 1. The functional activity of the C4F variants was investigated using a specific hemolytic overlay technique for C4. It was found that in almost all individuals (75 out of 78), the C4F 1 allele codes for a functionally inactive C4 product only when it occurs on an HLA-B17 positive haplotype but that the same allele codes for a functionally active fast variant of C4 when it occurs on an HLA-B37 positive haplotype (18 out of 18). Very strong genetic linkage disequilibrium was observed for the C4F 1 allele with HLA-B17 and B37. The active and inactive C4F 1 variant also has marked nonrandom gametic association to different alleles of the of locus and to HLA-C locus determinants. No further variants of the C4S (Chido) locus have been identified so far. Rodgers (Rg) typing by the plasma inhibition test of anti-Rg antiserum has shown that plasma from individuals homozygous for the C4F 1 allele is only able to partially inhibit anti-Rg whereas all C4F positive individuals totally inhibited the reaction.