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Infection and Immunity, April 2007, p. 1801-1810, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01758-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Impact of the Molecular Form of Immunoglobulin A on Functional Activity in Defense against Streptococcus pneumoniae{triangledown}

Claudine E. Fasching,1,2 Tracy Grossman,1,3 Blaise Corthésy,4 Andrew G. Plaut,5 Jeffrey N. Weiser,6 and Edward N. Janoff1,2,7*

Veterans Affairs Medical Center, Division of Infectious Disease and International Medicine, and Schools of,1 Medicine,2 Dentistry, University of Minnesota, Minneapolis, Minnesota,3 Division d'Immunologie et d'Allergie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland,4 Division of Gastroenterology and the GRASP Digestive Disease Center, Tufts-New England Medical Center Hospital, Tufts University School of Medicine, Boston, Massachusetts,5 Departments of Microbiology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,6 Division of Infectious Diseases, Colorado Center for AIDS Research, University of Colorado at Denver and Health Sciences Center, Denver Veterans Affairs Medical Center, Denver, Colorado7

Received 3 November 2006/ Returned for modification 5 December 2006/ Accepted 16 January 2007

Antibodies of the immunoglobulin A (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 IgA [mIgA], polymeric IgA [pIgA], and secretory IgA [SIgA]) on OPC and susceptibility to cleavage by IgA1 protease. The efficiency of SIgA in support of OPC of S. pneumoniae was comparable to that of pIgA, and both forms exceeded that of mIgA by a fivefold margin. This structure-function relationship was associated with three factors. First, the avidities, or functional affinities, of both pIgA and SIgA for pneumococcal capsules exceeded those of mIgA. Second, both pIgA and SIgA 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 SIgA. In summary, the polymeric forms of IgA (both pIgA and SIgA) provide a substantial advantage in binding, agglutination, and OPC of the organism.

* Corresponding author. Mailing address: Division of Infectious Diseases, Colorado CFAR, UCHSC, Room 1813, 4200 E. Ninth Ave., Denver, CO 80262. Phone: (303) 315-7233. Fax: (303) 315-8681. E-mail: Edward.Janoff{at}uchsc.edu.

{triangledown} Published ahead of print on 29 January 2007.

Editor: R. P. Morrison

Infection and Immunity, April 2007, p. 1801-1810, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01758-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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