The human IgA-Fc alpha receptor interaction and its blockade by streptococcal IgA-binding proteins.
IgA plays a key role in immune defence of the mucosal surfaces. IgA can trigger elimination mechanisms against pathogens through the interaction of its Fc region with Fc alpha Rs (receptors specific for the Fc region of IgA) present on neutrophils, macrophages, monocytes and eosinophils. The human Fc alpha R (CD89) shares homology with receptors specific for the Fc region of IgG (Fc gamma Rs) and IgE (Fc epsilon RIs), but is a more distantly related member of the receptor family. CD89 interacts with residues lying at the interface of the two domains of IgA Fc, a site quite distinct from the homologous regions at the top of IgG and IgE Fc recognized by Fc gamma R and Fc epsilon RI respectively. Certain pathogenic bacteria express surface proteins that bind to human IgA Fc. Experiments with domain-swap antibodies and mutant IgAs indicate that binding of three such proteins (Sir22 and Arp4 of Streptococcus pyogenes and beta protein of group B streptococci) depend on sites in the Fc interdomain region of IgA, the binding region also used by CD89. Further, we have found that the streptococcal proteins can inhibit interaction of IgA with CD89, and have thereby identified a mechanism by which a bacterial IgA-binding protein may modulate IgA effector function.
Department of Molecular and Cellular Pathology, University of Dundee Medical School, Ninewells Hospital, Dundee DD1 9SY, UK. j.m.woof@dundee.ac.uk
J M
JM
Woof
D015703:Antigens, CD / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology*; D008958:Models, Molecular; D011487:Protein Conformation; D011961:Receptors, Fc / Q000037:antagonists & inhibitors* / Q000276:immunology*
D015703:Antigens, CD; C062462:Arp4 protein, Streptococcus pyogenes; D001426:Bacterial Proteins; D002352:Carrier Proteins; C036832:Fc(alpha) receptor; C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc