Importance of the third thrombospondin repeat of C6 for terminal complement complex assembly.

The anti-C6 monoclonal antibody WU 6-4 was shown to be unequivocally native restricted since it neither binds to the terminal complement complex (TCC) nor to C5b6. In addition, it was shown to inhibit TCC formation by interfering with C5b6 generation. Using the pUEX expression system and C6 cDNA the WU 6-4 epitope was mapped to the third thrombospondin repeat of C6. This protein domain may therefore contribute to the C5 binding site of C6 and be involved in terminal complement complex assembly. The presence of the epitope in rabbit C6 indicates a useful model for studying inhibition of TCC formation in vivo.