Streptococcal IgA-binding proteins bind in the Calpha 2-Calpha 3 interdomain region and inhibit binding of IgA to human CD89.
Certain pathogenic bacteria express surface proteins that bind to the Fc part of human IgA or IgG. These bacterial proteins are important as immunochemical tools and model systems, but their biological function is still unclear. Here, we describe studies of three streptococcal proteins that bind IgA: the Sir22 and Arp4 proteins of Streptococcus pyogenes and the unrelated beta protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Calpha2/Calpha3 domain interface are critical for binding of the streptococcal proteins. This region is also used in binding the human IgA receptor CD89, an important mediator of IgA effector function. In agreement with this finding, the three IgA-binding proteins and a 50-residue IgA-binding peptide derived from Sir22 blocked the ability of IgA to bind CD89. Further, the Arp4 protein inhibited the ability of IgA to trigger a neutrophil respiratory burst via CD89. Thus, we have identified residues on IgA-Fc that play a key role in binding of different streptococcal IgA-binding proteins, and we have identified a mechanism by which a bacterial IgA-binding protein may interfere with IgA effector function.
Pleass
R J
RJ
Department of Molecular and Cellular Pathology, University of Dundee Medical School, Ninewells Hospital, Dundee DD1 9SY, United Kingdom.
Areschoug
T
T
Lindahl
G
G
Woof
J M
JM
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D008969:Molecular Sequence Data; D011961:Receptors, Fc / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000737:chemistry*
D015703:Antigens, CD; D001426:Bacterial Proteins; D002352:Carrier Proteins; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc