Complement activation by individual and combinations of monoclonal antibodies to Actinomyces viscosus T14V fimbriae: a probe for epitope distribution on these polymeric proteins.
The spatial requirements for IgG activation of the classical complement pathway has provided a basis for utilizing complement consumption by individual and pairs of monoclonal antibodies (mAbs) to compare the repeating epitope patterns of the type 1 and type 2 fimbriae of Actinomyces viscosus T14V and to examine the co-operative effects of mAbs against these polymeric proteins. Three of five mAbs specific for the type 1 fimbriae consumed complement when assayed individually. Four patterns of complement consumption were detected with pairs of these mAbs: inhibition, addition, enhancement or synergy. Inhibition occurred when both members of a pair reacted with the same epitope but only one consumed complement. A strictly additive effect was observed if both mAbs consumed complement and, in addition, recognized the same epitope. Complement consumption by mAbs against certain epitopes was enhanced by non-complement consuming mAbs that reacted with different epitopes. Synergy was observed with extremely low concentrations of two mAbs each of which reacted with a different epitope and consumed complement. In contrast to the anti-type 1 mAbs, only one of seven mAbs against the type 2 fimbriae consumed more than 20% of the available complement. Pairs of anti-type 2 mAbs exhibited only inhibition or synergy. The latter effect was particularly striking as pairs containing mAbs that reacted with different epitopes and failed to consume complement or were minimally active when assayed individually were extremely efficient. These data indicated that the spatial arrangements of individual mAbs bound to repeating epitopes in the type 1, but not the type 2, fimbriae were appropriate for activation of complement. Thus, the repeating epitope patterns of the two types of fimbriae apparently differ.
Laboratory of Microbial Ecology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
A L
AL
Sandberg
J O
JO
Cisar
R P
RP
Siraganian
L L
LL
Mudrick
M W
MW
Armstrong
D000190:Actinomyces / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D001704:Biopolymers; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D010861:Fimbriae, Bacterial / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments; D051379:Mice
D000911:Antibodies, Monoclonal; D001704:Biopolymers; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D003165:Complement System Proteins