The anti-C6 monoclonal antibody WU 6-4 was shown to be unequivocally n
ative restricted since it neither binds to the terminal complement com
plex (TCC) nor to C5b6. In addition, it was shown to inhibit TCC forma
tion by interfering with C5b6 generation. Using the pUEX expression sy
stem and C6 cDNA the WU 6-4 epitope was mapped to the third thrombospo
ndin repeat of CG. 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.