Different HLA antigen associations for the functionally active and inactive products of the complement C4F1 allele

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 C4F1 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, C4Fo, and C4F1. 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 C4F1 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 HLS-B37 positive haplotype (18 out of 18). Very strong genetic linkage disequilibrium was observed for the C4F1 allele with HLA-B17 and B37. The active and inactive C4F1 variant also has marked nonrandom gametic association to different alleles of the Bf 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 C4F1 allele is only able to partially inhibit anti-Rg whereas all C4F positive individuals totally inhibited the reaction.