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Infect Immun, April 1998, p. 1538-1546, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Characterization of Anticapsular Monoclonal
Antibodies That Regulate Activation of the Complement System by the
Cryptococcus neoformans Capsule
Thomas R.
Kozel,*
Bouke C. H.
deJong,
Matthew M.
Grinsell,
Randall S.
MacGill, and
Kevin K.
Wall
Department of Microbiology and Cell and
Molecular Biology Program, School of Medicine, University of Nevada,
Reno, Nevada 89557
Received 12 September 1997/Returned for modification 16 October
1997/Accepted 25 November 1997
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 (MAbs) specific for different epitopes of the
major capsular polysaccharide to alter the kinetics for classical and alternative pathway-mediated deposition of C3 onto a serotype A strain.
We studied MAbs reactive with 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 groupings are based on antibody variable region
usage which determines the antibody molecular structure. When both the
classical and alternative pathways were operative, group II MAbs
induced early classical pathway-mediated binding of C3 but reduced the
overall rate of C3 accumulation and the amount of bound C3. Group III
MAbs closely mimicked the effects of group II MAbs but exhibited
reduced support of early classical pathway-facilitated accumulation of
C3. Depending on the antibody isotype, group IV MAbs slightly or
markedly enhanced early binding of C3 but had no effect on either the
rate of C3 accumulation or the amount of bound C3. When the classical
pathway was blocked, group II and III MAbs markedly suppressed C3
binding that normally would have occurred via the alternative pathway. In contrast, MAbs of group IV had no effect on alternative
pathway-mediated C3 binding. These results indicate that anticapsular
antibodies with different epitope specificities may have distinct
regulatory effects on activation and binding of C3.
*
Corresponding author. Mailing address: Department of
Microbiology/320, School of Medicine, University of Nevada, Reno, NV 89557. Phone: (702) 784-6161. Fax: (702) 784-1620. E-mail:
trkozel{at}med.unr.edu.
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