Antigenic determinants of human C4, Rodgers and Chido.

The duplicated genes, C4A and C4B, are located within the major histocompatibility complex on chromosome 6 and each exhibits a high degree of polymorphism expressed as both electrophoretic and antigenic variation (Rg/Ch). Eight high-frequency antigens and one low-frequency antigen have been defined by immune human polyspecific antisera in haemagglutination inhibition assays. Close association exists between different C4 allotypes and the antigens they express. Normally, C4A expresses Rg and C4B has Ch but rare reverse associations exist. Nucleotide sequences of the C4d region from C4 allotypes of known antigenic status have demonstrated four polymorphic sites that correlate with the antigens, which, in a structural model, are seen to be conformational or sequential epitopes. The observed interrelationships of the antigens on C4 allotypes accommodated by the model suggest that the electrophoretic variation is located outside the C4d region. The molecular genetics of C4 are also considered as part of the polymorphism.