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Infect Immun, April 1998, p. 1547-1553, Vol. 66, No. 4
Department of Microbiology and the Cell and
Molecular Biology Program, School of Medicine, University of Nevada,
Reno, Nevada 89557
Received 12 September 1997/Returned for modification 27 October
1997/Accepted 9 January 1998
Encapsulated cells of Cryptococcus neoformans are
potent activators of the alternative complement pathway. Previous
studies found that monoclonal antibodies (MAbs) specific for the major capsular polysaccharide, termed glucuronoxylomannan (GXM), can markedly
suppress the ability of the capsule to accumulate C3 from normal human
serum via the alternative pathway. The present study examined the
abilities of F(ab)2 and Fab fragments of three MAbs (MAbs
439, 3C2, and 471) to mediate the suppressive effect. The results
showed that F(ab)2 fragments of all three MAbs suppressed activation and binding of C3 via the alternative pathway in a manner
similar to that of intact antibodies. In contrast, Fab fragments of MAb
439 and MAb 3C2 showed no suppressive activity, and Fab fragments of
MAb 471 were markedly reduced in suppressive activity. Indeed, there
was an earlier accumulation of C3 on encapsulated cryptococci in the
presence of the Fab fragments. Study of subclass switch families of MAb
439 and MAb 471 found that MAbs of an immunoglobulin G (IgG) subclass
with increased flexibility in the hinge region (IgG2b) had less
suppressive activity than MAbs of IgG subclasses with less flexibility
(IgG1 or IgG2a). Taken together, these results indicate that
cross-linking of the capsular matrix is an essential component in
suppression of the alternative complement pathway by anti-GXM MAbs.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Bivalency Is Required for Anticapsular Monoclonal
Antibodies To Optimally Suppress Activation of the Alternative
Complement Pathway by the Cryptococcus neoformans
Capsule
*
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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