Mediation and Modulation of Antibody Function

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 FcaRs (receptors specific for the Fc region of IgA) present on neutrophils, macrophages, monocytes and eosinophils. The human FcaR (CD89) shares homology with receptors specific for the Fc region of IgG (FcyRs) and IgE (FceRIs), 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 FcyR and FcsRI 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 p 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. The role of human IgA in immunity Human IgA is the most abundant antibody class in the body. The daily production of IgA, estimated to be of the order of 65 mg/kg, far exceeds that of the other antibody classes combined [l]. IgA is an important serum antibody, but perhaps plays its most important role as the major Ig in the seromucous secretions that bathe mucosal surfaces such as those of the tracheobronchial, gastrointestinal and genito-urinary tracts. These tracts