Impact of the molecular form of immunoglobulin A on functional activity in defense against Streptococcus pneumoniae.
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.
Fasching
Claudine E
CE
Division of Infectious Diseases and International Medicine, Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN, USA.
Grossman
Tracy
T
Corthésy
Blaise
B
Plaut
Andrew G
AG
Weiser
Jeffrey N
JN
Janoff
Edward N
EN
D000371:Agglutination / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity; D016667:Bacterial Capsules / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000276:immunology / Q000378:metabolism; D011008:Pneumococcal Infections / Q000276:immunology*; D012697:Serine Endopeptidases / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013329:Structure-Activity Relationship
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D003165:Complement System Proteins; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase