CHARACTERIZATION OF ANTICAPSULAR MONOCLONAL-ANTIBODIES THAT REGULATE ACTIVATION OF THE COMPLEMENT-SYSTEM BY THE CRYPTOCOCCUS-NEOFORMANS CAPSULE

Incubation of the encapsulated yeast Cryptococcus neoformans in human serum leads to alternative pathway-mediated deposition of C3 fragments in the capsule. We examined the ability of monoclonal antibodies (MAb s) specific for different epitopes of the major capsular polysaccharid e to alter the kinetics for classical and alternative pathway-mediated deposition of C3 onto a serotype A strain. We studied MAbs reactive w ith capsular serotypes A, B, C, and D (MAb group II); serotypes A, B, and D (MAb group III); and serotypes A and D (MAb group IV), The MAb g roupings are based on antibody variable region usage which determines the antibody molecular structure. When both the classical and alternat ive pathways were operative, group II MAbs induced early classical pat hway-mediated binding of C3 but reduced the overall rate of C3 accumul ation and the amount of bound C3, Group III MAbs closely mimicked the effects of group II MAbs but exhibited reduced support of early classi cal pathway-facilitated accumulation of C3, Depending on the antibody isotype, group TV MAbs slightly or markedly enhanced early binding of C3 but had no effect on either the rate of C3 accumulation or the amou nt of bound C3, When the classical pathway was blocked, group II and I n. MAbs markedly suppressed C3 binding that normally would have occurr ed via the alternative pathway, In contrast, MAbs of group TV had no e ffect on alternative pathway-mediated C3 binding. These results indica te that anticapsular antibodies with different epitope specificities m ay have distinct regulatory effects on activation and binding of C3.