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Infect. Immun. doi:10.1128/IAI.01758-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Impact of the Molecular Form of IgA on Functional Activity in Defense Against Streptococcus pneumoniae

Veterans Affairs Medical Center, Division of Infectious Disease and International Medicine, Schools of Medicine and Dentistry, University of Minnesota, Minneapolis, Minnesota; Division dImmunologie et dAllergie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Division of Gastroenterology and the GRASP Digestive Disease Center, Tufts-New England Medical Center Hospital, Tufts University School of Medicine. Boston, Massachusetts; Departments of Microbiology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Division of Infectious Diseases, Colorado Center for AIDS Research, University of Colorado at Denver and Health Sciences Center, Denver Veterans Affairs Medical Center, Denver, Colorado

^* To whom correspondence should be addressed. Email: Edward.Janoff{at}uchsc.edu.

	Abstract

Antibodies of the IgA class react with capsular polysaccharides of Streptococcus pneumoniae and support complement-dependent opsonophagocytosis (OPC) of the organism by phagocytes. We characterized the biologic impact of the molecular forms of human monoclonal capsule-specific IgA (monomeric [mIgA], polymeric IgA [pIgA], and secretory IgA [SIgA]) on OPC and susceptibility to cleavage by IgA1 protease. The efficiency of SIgA to support OPC of S. pneumoniae was comparable to that of pIgA and both forms exceeded that of mIgA by 5 fold. This structure-function relationship was associated with three factors. First, the avidities, or functional affinities, of both pIgA and SIgA for pneumococcal capsules exceeded that of mIgA. Second, both pIgA and S-IgA required less complement to achieve similar levels of bacterial OPC than did mIgA, indicating that secretory component does not hinder the effect of complement. Third, both pIgA and SIgA mediated agglutination of the organism, whereas mIgA did not. All three forms of capsule-specific IgA showed comparable susceptibilities to cleavage and functional inhibition by bacterial IgA1 protease, demonstrating that secretory component does not prevent the proteolytic degradation of IgA1 by IgA1 protease. IgA1 cleavage results in formation of identical Fab fragments for each of the molecular forms, thereby abolishing the contribution of multivalence of pIgA and S-IgA. In summary, the polymeric forms of IgA (both pIgA and SIgA) provide a substantial advantage in binding, agglutination and OPC of the organism.