Molecular characteristics of IgA and IgM Fc binding to the Fcα/μR

Fcα/μ receptor (Fcα/μR), a novel Fc receptor for IgA and IgM, is a type I transmembrane protein with an immunoglobulin (Ig)-like domain in the extracellular portion. Although IgA and IgM bind to Fcα/μR, the molecular and structural characteristics of the ligand-receptor interactions have been undetermined. Here, we developed twelve monoclonal antibodies (mAbs) against murine Fcα/μR by immunizing mice deficient in Fcα/μR gene. Eight mAbs totally or partially blocked IgA and IgM bindings to Fcα/μR. These blocking mAbs bound to a peptide derived from the Ig-like domain of murine Fcα/μR, which is conserved not only in human and rat Fcα/μR but also in polymeric Ig receptor (poly-IgR), another Fc receptor for IgA and IgM. These results suggest that IgA and IgM bind to an epitope in the conserved amino acids in the Ig-like domain of Fcα/μR as well as poly-IgR.