Fc alpha receptor

The Fc alpha receptor I is the high-affinity receptor for monomeric IgA1 and IgA2. The receptor binds the Fc domain of IgA via the extracellular EC1 domain. Activation can trigger proinflammatory reactions such as phagocytosis, cytokine release, oxidative burst, antibody-associated cell-mediated cytotoxicity.

The receptor or its different isoforms (A.1., A.2., A.3) are expressed on the surface of mucosal monocytes, macrophages, alveolar macrophages, neutrophils and eosinophils.

IgA plays an important role in the immune defense of mucosal surfaces. IgA can trigger elimination mechanisms against pathogens through the interaction of its Fc region with Fc-alpha receptors (receptors specific for the Fc region of IgA) on neutrophils, macrophages, monocytes and eosinophils. The human Fc-alpha-R (CD89) has homology to receptors specific for the Fc region of IgG (Fc-gamma-Rs) and IgE (Fc-epsilon-RIs), but is a more distant member of the receptor family.

CD89 interacts with residues located at the interface of the two domains of IgA Fc, a site that is distinctly different from the homologous regions at the tip of IgG and IgE Fc, which are recognized by Fc-gamma-R and Fc-epsilon-RI, respectively.

Certain pathogenic bacteria express surface proteins that bind to human IgA Fc. These include the Sir22 and Arp4 proteins of Streptococcus pyogenes and the beta protein of group B streptococci. This binding depends on sites in the Fc interdomain region of IgA, a binding region also utilized by CD89 (Woof JM 2002).

1. Woof JM (2002) The human IgA-Fc alpha receptor interaction and its blockade by streptococcal IgA-binding proteins. Biochem Soc Trans 30:491-494.