TY - JOUR
T1 - Streptococcal IgA-binding Proteins Bind in the Cα2-Cα3 Interdomain Region and Inhibit Binding of IgA to Human CD89
AU - Pleass, Richard J.
AU - Areschoug, Thomas
AU - Lindahl, Gunnar
AU - Woof, Jenny M.
PY - 2001/3/16
Y1 - 2001/3/16
N2 - 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 β protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Cα2/Cα3 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.
AB - 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 β protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Cα2/Cα3 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.
UR - http://www.scopus.com/inward/record.url?scp=0035896552&partnerID=8YFLogxK
U2 - 10.1074/jbc.M009396200
DO - 10.1074/jbc.M009396200
M3 - Article
C2 - 11096107
AN - SCOPUS:0035896552
SN - 0021-9258
VL - 276
SP - 8197
EP - 8204
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 11
ER -