The polymorphism of the complement genes in HLA.

Genes coding for the complement proteins C2, C4A, C4B and factor B lie between HLA-D and HLA-B in HLA, the major histocompatibility complex in man. All the complement components are polymorphic, particularly C4, which has many alleles at each locus. The genetic complexity of C4 extends to the number of loci each of which may be deleted or duplicated on the chromosome. The different forms of C4 showed markedly different reactivities with small molecules and on haemolytic activity in the complement system. Surprisingly, amino acid sequences of the several allelic forms of C4 appear to be very similar, with less than 1% of residue positions being changed between alleles of C4A and C4B. These results may be relevant to the increased susceptibility to autoimmune disease which is associated with particular haplotypes of the HLA complex.